Mar 2011

PNN Quarterly File—First Quarter 2011

PNN Pharmacotherapy Line
Jan. 3, 2011 * Vol. 18, No. 1
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Jan. 1 issue of Lancet (2011; 377).
ASA & Cancer Mortality: Daily administration of aspirin, even in low doses, for 5 years or more reduces risks of several types of solid tumors, including those occurring in the gastrointestinal tract and other parts of the body, according to an analysis of individual patient data from long-term trials (pp. 31–41). Researchers obtained data from randomized trials of daily versus no aspirin lasting 4 years or longer. Follow-up data were found on U.K. death certificates and in cancer registries, with these results: “In eight eligible trials (25,570 patients, 674 cancer deaths), allocation to aspirin reduced death due to cancer (pooled odds ratio [OR] 0.79, 95% CI 0.68–0.92, p = 0.003). On analysis of individual patient data, which were available from seven trials (23,535 patients, 657 cancer deaths), benefit was apparent only after 5 years’ follow-up (all cancers, hazard ratio [HR] 0.66, 0.50–0.87; gastrointestinal cancers, 0.46, 0.27–0.77; both p = 0.003). The 20-year risk of cancer death (1,634 deaths in 12,659 patients in three trials) remained lower in the aspirin groups than in the control groups (all solid cancers, HR 0.80, 0.72–0.88, p < 0.0001; gastrointestinal cancers, 0.65, 0.54–0.78, p < 0.0001), and benefit increased (interaction p = 0.01) with scheduled duration of trial treatment (≥7.5 years: all solid cancers, 0.69, 0.54–0.88, p = 0.003; gastrointestinal cancers, 0.41, 0.26–0.66, p = 0.0001). The latent period before an effect on deaths was about 5 years for oesophageal, pancreatic, brain, and lung cancer, but was more delayed for stomach, colorectal, and prostate cancer. For lung and oesophageal cancer, benefit was confined to adenocarcinomas, and the overall effect on 20-year risk of cancer death was greatest for adenocarcinomas (HR 0.66, 0.56–0.77, p < 0.0001). Benefit was unrelated to aspirin dose (75 mg upwards), sex, or smoking, but increased with age—the absolute reduction in 20-year risk of cancer death reaching 7.08% (2.42–11.74) at age 65 years and older.” (P. M. Rothwell, peter.rothwell@clneuro.ox.ac.uk)
Rituximab Maintenance Therapy in Follicular Lymphoma: Following immunochemotherapy as first-line treatment of follicular lymphoma, 2 years of maintenance therapy with rituximab significantly improves progression-free survival (PFS), researchers report (pp. 42–51). In the randomized, open-label PRIMA study at 223 centers in 25 countries, 1,215 patients with previously untreated follicular lymphoma had these responses to rituximab after receiving one of three induction regimens used in routine clinical practice: “505 patients were assigned to rituximab maintenance and 513 to observation (one patient died during randomisation). With a median follow-up of 36 months (IQR 30–42), PFS was 74.9% (95% CI 70.9–78.9) in the rituximab maintenance group (130 patients progressed) and 57.6% (53.2–62.0) in the observation group (218 progressed; hazard ratio [HR] 0.55, 95% CI 0.44–0.68, p < 0.0001). 2 years after randomisation, 361 patients (71.5%) in the rituximab maintenance group were in complete or unconfirmed complete response versus 268 (52.2%) in the observation group (p = 0.0001). Overall survival did not differ significantly between groups (HR 0.87, 95% CI 0.51–1.47). Grade 3 and 4 adverse events were recorded in 121 patients (24%) in the rituximab maintenance group and 84 (17%) in the observation group (risk ratio 1.46, 95% CI 1.14–1.87; p = 0.0026). Infections (grades 2–4) were the most common adverse event, occurring in 197 (39%) and 123 (24%) patients, respectively (risk ratio 1.62, 95% CI 1.35–1.96; p < 0.0001).” (G. Salles, gilles.salles@chu-lyon.fr)

>>>PNN NewsWatch
* Fruta Planta weight loss products contain undeclared sibutramine, FDA warned on Thursday.

>>>PNN JournalWatch
* General Anesthesia, Sleep, and Coma, in New England Journal of Medicine, 2010; 363: 2638–50. (E. N. Brown, enb@neurostat.mit.edu)
* Dose Response of Inhaled Corticosteroids in Children with Persistent Asthma: A Systematic Review, in
Pediatrics, 2011; 127: 129–138. (L. Zhang)
* Heart Failure Caused by Molecularly Targeted Therapies for Cancer, in
Pharmacotherapy, 2011; 31: 62–75. (A. Jarkowski, III, Anthony.Jarkowski@roswellpark.org)
* Valvular Heart Disease: A Primer for the Clinical Pharmacist, in
Pharmacotherapy, 2011; 31: 76–91. (T. J. Bungard, tammy.bungard@ualberta.ca)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Jan. 4, 2011 * Vol. 18, No. 2
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Jan. 4 issue of the Annals of Internal Medicine (2011; 154).
Treatment for Retroperitoneal Fibrosis: In a case series of 28 patients with retroperitoneal fibrosis, the combination of prednisone and mycophenolate mofetil showed sufficient evidence of effectiveness to warrant testing in randomized trials, researchers report (pp. 31-6). The prospective series ran from 2005 to 2009 at a single tertiary-care facility, providing these results for prednisone 40 mg/d tapered over 6 months and mycophenolate mofetil 1000 mg twice daily over a mean of 24.3 months: “Systemic symptoms resolved in all patients; 89% had a 25% or greater reduction in periaortic mass. Elevated erythrocyte sedimentation rate and serum creatinine level and decreased hemoglobin level normalized in all patients. Disease recurred in 2 of 28 patients.”
The authors conclude: “Although the ideal agents have yet to be defined, this report confirms and expands on our initial observation that a combination of prednisone and [mycophenolate mofetil] can alleviate the symptoms (weight loss, pain, and fatigue) and correct the laboratory abnormalities (in erythrocyte sedimentation rate and hemoglobin and serum creatinine levels) associated with [retroperitoneal fibrosis]. This pharmacologic combination can also result in a measurable decrease in the periaortic mass characteristic of this disease and allows the eventual removal of ureteral stents in patients with associated ureteric obstruction.” (P. J. Scheel Jr.,
PScheel1@jhmi.edu)
Cost-Effectiveness of Dabigatran in Atrial Fibrillation: The dabigatran cost-effectiveness analysis released in advance (see PNN, Nov. 2) is published in this issue (pp. 1–11). “Dabigatran may be a cost-effective alternative to warfarin depending on pricing in the United States,” the authors conclude, citing their analysis of patients aged 65 years or older with nonvalvular atrial fibrillation who have CHADS2 scores of 1 or greater, indicating increased stroke risk.
The investigators conclude: “High-dose dabigatran was the most cost-effective and most effective therapy we evaluated, providing an additional 0.56 [quality-adjusted life–years] over warfarin in our base-case analysis. For patients at higher risk for ischemic stroke and [intracranial hemorrhage], the [incremental cost-effectiveness ratio] of dabigatran compared with warfarin improved. These results were robust over a wide range of model assumptions but were sensitive to dabigatran costs.” (M. Turakhia,
mintu@stanford.edu)
Educating Physicians About Addiction Medicine: “The time has come” for incorporating addiction medicine into graduate medical education, write authors of a article that describes experiences at the Betty Ford Institute (pp. 56–9). “Experts … developed the following 5 recommendations focused on improving training in substance abuse in primary care residency programs in internal medicine and family medicine: 1) integrating substance abuse competencies into training, 2) assigning substance abuse teaching the same priority as teaching about other chronic diseases, 3) enhancing faculty development, 4) creating addiction medicine divisions or programs in academic medical centers, and 5) making substance abuse screening and management routine care in new models of primary care practice. This enhanced primary care residency training should represent a major step forward in improving patient care.” (P. G. O’Connor, patrick.oconnor@yale.edu)

>>>PNN NewsWatch
* FDA yesterday announced two product recalls via the MedWatch system. Cumberland Pharmaceuticals has recalled 6 lots of Acetadote (acetylcysteine) Injection, 20% solution (200 mg/mL) in 30-mL single dose glass vials as a precautionary measure based on observed particulate matter found in a very small number of vials, FDA said. The source of the particulate matter was from the glass vial produced by a former supplier. FDA also said that the Ritedose Corporation is conducting a voluntary recall of 0.083% Albuterol Sulfate Inhalation Solution, 3 mL in 25, 30, and 60 unit dose vials. This product is being recalled because the 2.5 mg/3 mL single use vials are embossed with the wrong concentration of 0.5 mg/ 3 mL. Only the unit dose vials are incorrectly embossed as containing 0.5 mg/3 mL. The correct concentration of 2.5 mg/3 mL is labeled on the primary foil overwrap pouches and shelf cartons.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Jan. 5, 2011 * Vol. 18, No. 3
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Jan. 5 issue of JAMA (2011; 305).
Botulinum Neurotoxin Terminology: The author of a Commentary, after reflecting on the “almost unpronounceable new names” of the botulinum neurotoxins marketed in the U.S., explores other potential problems in practice with onabotulinumtoxinA (Botox), rimabotulinumtoxinB (Myobloc), abobotulinumtoxinA (Dysport), and incobotulinumtoxinA (Xeomin) (pp. 89–90): “The availability of multiple products of botulinum neurotoxins type A may bring to the United States a number of practical problems already observed in Europe. Switching between one brand of botulinum neurotoxins with another occurs regularly in different European centers, mainly because of restricted availability and labeling differences. Due to overlapping indications, hospital managers may choose to purchase only one formulation of botulinum neurotoxins. If patients move from one center to another, in which physicians preferentially use a toxin brand different from the one the patient previously received, variations in outcome may be perceived. Each product of botulinum neurotoxins is measured with proprietary units that are considered to be noninterchangeable. With the only possible exception of the asserted equivalence of incobotulinumtoxinA and onabotulinumtoxinA units for patients with cervical dystonia,​ there is no unique dose ratio to allow switching from one toxin brand to another even for a single indication.” (A. Albanese, alberto.albanese@unicatt.it)
Management of Chronic Prostatitis: Alpha-blockers, antibiotics, and combinations of these drugs are useful in management of chronic prostatitis and chronic pelvic pain syndrome, according to a systematic review and meta-analysis of comparative randomized controlled trials (pp. 78–86). Authors note these results from 23 studies: “Compared with placebo, alpha-blockers were associated with significant improvement in symptoms with standardized mean differences in total symptom, pain, voiding, and quality-of-life scores of −1.7 (95% confidence interval [CI], −2.8 to −0.6), −1.1 (95% CI, −1.8 to −0.3), −1.4 (95% CI, −2.3 to −0.5), and −1.0 (95% CI, −1.8 to −0.2), respectively. Patients receiving alpha-blockers or anti-inflammatory medications had a higher chance of favorable response compared with placebo, with pooled RRs of 1.6 (95% CI, 1.1-2.3) and 1.8 (95% CI, 1.2-2.6), respectively. Contour-enhanced funnel plots suggested the presence of publication bias for smaller studies of alpha-blocker therapies. The network meta-analysis suggested benefits of antibiotics in decreasing total symptom scores (−9.8; 95% CI, −15.1 to −4.6), pain scores (−4.4; 95% CI, −7.0 to −1.9), voiding scores (−2.8; 95% CI, −4.1 to −1.6), and quality-of-life scores (−1.9; 95% CI, −3.6 to −0.2) compared with placebo. Combining alpha-blockers and antibiotics yielded the greatest benefits compared with placebo, with corresponding decreases of −13.8 (95% CI, −17.5 to −10.2) for total symptom scores, −5.7 (95% CI, −7.8 to −3.6) for pain scores, −3.7 (95% CI, −5.2 to −2.1) for voiding, and −2.8 (95% CI, −4.7 to −0.9) for quality-of-life scores.” (A. Thakkinstian, raatk@mahidol.ac.th)
Regenerating Damaged Limbs: Newts and zebrafish can do it—so why can’t humans grow new limbs when one is damaged? That question is explored in a Commentary on the evolutionary aspects of regenerative medicine (pp. 87–8). “Transient inhibition of tumor suppressors might play a role,” the authors write. “It has been postulated that during evolution mammals lost regenerative potential as a trade-off for cancer protection. The tumor suppressor Rb, encoded by the retinoblastoma gene, is known as the eukaryotic ‘gatekeeper’ of the cell cycle G1-S transition. Inactivation of Rb mediates newt regeneration.​ In contrast, loss of Rb does not lead to mammalian cell dedifferentiation (eg, primary skeletal muscle cells).”
The writers conclude: “The re“evolutionary” approach to regenerative medicine, the transient dual knockdown of tumor suppressors, ARF and Rb, addresses one critical obstacle to translating the potent regenerative capabilities of newts to mammals. The adaptation of a mechanism that nature has previously designed and successfully exploited is highly appealing. Dedifferentiation may provide insights into human disease, lead to drug discovery, and a means for regenerating tissues. Perhaps newts can give humans, as well as themselves, a hand.” (H. M. Blau,
hblau@stanford.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Jan. 6, 2011 * Vol. 18, No. 4
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 6 issue of the New England Journal of Medicine (2011; 364).
Eplerenone in Systolic Heart Failure: In 2,737 patients with mild systolic heart failure, eplerenone significantly reduced mortality and hospitalization rates in a trial shortened because of the drug’s effectiveness (pp. 11–21). Participants in the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF), all of whom had New York Heart Association class II heart failure and an ejection fraction of 35% or less, received eplerenone in doses of up to 50 mg daily or placebo. Results showed: “The trial was stopped prematurely, according to prespecified rules, after a median follow-up period of 21 months. The primary outcome occurred in 18.3% of patients in the eplerenone group as compared with 25.9% in the placebo group (hazard ratio, 0.63; 95% confidence interval [CI], 0.54 to 0.74; P < .001). A total of 12.5% of patients receiving eplerenone and 15.5% of those receiving placebo died (hazard ratio, 0.76; 95% CI, 0.62 to 0.93; P = 0.008); 10.8% and 13.5%, respectively, died of cardiovascular causes (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P = 0.01). Hospitalizations for heart failure and for any cause were also reduced with eplerenone. A serum potassium level exceeding 5.5 mmol per liter occurred in 11.8% of patients in the eplerenone group and 7.2% of those in the placebo group (P < 0.001).” (F. Zannad, f.zannad@chu-nancy.fr)
Are aldosterone antagonists the “last man standing” in treatment of heart failure? An editorialist believes so (
pp. 79–80): “The EMPHASIS-HF investigators have added real value to the management of heart failure. Since spironolactone is available for pennies a day, one might reasonably ask whether the greater cost of eplerenone is warranted or whether it is reasonable to simply assume that the current findings also apply to spironolactone and reserve the newer, more expensive therapy for those few patients in whom the side effects of spironolactone are disabling. I believe this would be a reasonable tactic. It is now time to overcome undertreatment by ensuring that this form of therapy is incorporated into all heart-failure regimens. It is incumbent on the prescriber to perform appropriate monitoring of renal and electrolyte status, which can enhance the safety of such treatment.” (P. W. Armstrong)
Rifaximin for Irritable Bowel Syndrome Without Constipation: In the TARGET 1 and 2 trials, patients have significantly fewer symptoms of irritable bowel syndrome when treated with rifaximin for as little as 2 weeks, researchers report (pp. 22–32). The identically designed studies included 1,260 patients with IBS without constipation produced these results: “Significantly more patients in the rifaximin group than in the placebo group had adequate relief of global IBS symptoms during the first 4 weeks after treatment (40.8% vs. 31.2%, P = 0.01, in TARGET 1; 40.6% vs. 32.2%, P = 0.03, in TARGET 2; 40.7% vs. 31.7%, P < 0.001, in the two studies combined). Similarly, more patients in the rifaximin group than in the placebo group had adequate relief of bloating (39.5% vs. 28.7%, P = 0.005, in TARGET 1; 41.0% vs. 31.9%, P = 0.02, in TARGET 2; 40.2% vs. 30.3%, P < 0.001, in the two studies combined). In addition, significantly more patients in the rifaximin group had a response to treatment as assessed by daily ratings of IBS symptoms, bloating, abdominal pain, and stool consistency. The incidence of adverse events was similar in the two groups.” (W. P. Forbes)
As FDA considers whether to approve this antibiotic for treatment of IBS, clinicians should remain cautious, an editorialist advises (
pp. 81–2): “With three studies confirming the efficacy of the drug after a short-term regimen and a relatively short follow-up period, rifaximin has the potential to provide a welcome addition to the limited armamentarium of agents that are available to treat IBS. Moreover, rifaximin had a favorable safety profile in these studies, with no treatment-associated major adverse events and no cases of C. difficile colitis. At the current stage of knowledge, however, clinicians should proceed with caution. IBS is a chronic condition, and some regulatory authorities recommend that studies be conducted that will address the efficacy of rifaximin when it is used for continued or intermittent treatment of IBS (see www.tga.gov.au/docs/pdf/euguide/ewp/078597en.pdf), and this seems to be even more appropriate in the case of antibiotic therapy that may have a risk of inducing resistance over time.” (J. Tack)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Jan. 7, 2011 * Vol. 18, No. 5
Providing news and information about medications and their proper use

>>>Circulation Highlights
Source:
Early-release article from and Jan. 4 issue of Circulation (2011; 123).
Management of Atrial Fibrillation: New guidelines for management of atrial fibrillation are published, but they do not include the recently approved dabigatran (pp. 104–23). The guidelines include sections on management of rate control during AF and maintenance of sinus rhythm. A new process should result in a dabigatran update soon, the authors note: “In an effort to respond promptly to new evidence, the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) Task Force on Practice Guidelines has created a ‘focused update’ process to revise the existing guideline recommendations that are affected by the evolving data or opinion. Before the initiation of this focused approach, periodic updates and revisions of existing guidelines required up to 3 years to complete. Now, however, new evidence will be reviewed in an ongoing fashion to more efficiently respond to important science and treatment trends that could have a major impact on patient outcomes and quality of care. Evidence will be reviewed at least twice a year, and updates will be initiated on an as-needed basis and completed as quickly as possible while maintaining the rigorous methodology that the ACCF and AHA have developed during their partnership of more than 20 years.” (843-216-2533; kelle.ramsay@wolterskluwer.com)
Dabigatran in Cardioversion: Dabigatran was a “reasonable alternative to warfarin” in patients with nonvalvular atrial fibrillation who were undergoing cardioversion, report researchers who analyzed data from the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial (CIRCULATIONAHA.110.977546). The study compared dabigatran 110 mg twice daily (D110) and 150 mg twice daily (D150) with warfarin for stroke prevention in 18,113 patients, with these results for cardioversion: “A total of 1,983 cardioversions were performed in 1,270 patients: 647, 672, and 664 in the D110, D150, and warfarin groups, respectively. For D110, D150, and warfarin, transesophageal echocardiography was performed before 25.5%, 24.1%, and 13.3% of cardioversions, of which 1.8%, 1.2%, and 1.1% were positive for left atrial thrombi. Continuous treatment with study drug for 3 weeks before cardioversion was lower in D110 (76.4%) and D150 (79.2%) compared with warfarin (85.5%; P < 0.01 for both). Stroke and systemic embolism rates at 30 days were 0.8%, 0.3%, and 0.6% (D110 versus warfarin, P = 0.71; D150 versus warfarin, P = 0.40) and similar in patients with and without transesophageal echocardiography. Major bleeding rates were 1.7%, 0.6%, and 0.6% (D110 versus warfarin, P = 0.06; D150 versus warfarin, P = 0.99).” (M. D. Ezekowitz, ezekowitzm@mlhs.org)
Anticoagulation in Ross Procedure Patients: Investigators found no late survival difference during 10 years of monitoring of patients who had undergone the Ross procedure or had mechanical valve replacement for diseased aortic valves (pp. 31–8). In the Ross procedure, the aortic valve is replaced with the patient’s own pulmonary valve, which in turn is replaced with a cadaveric pulmonary valve. Optimal self-management anticoagulation probably played a role in these positive late-survival results, the authors concluded: “Two hundred fifty-three patients with a mechanical valve (mean follow-up, 6.3 years) could be propensity matched to a Ross patient (mean follow-up, 5.1 years). Mean age of the matched cohort was 47.3 years in the Ross procedure group and 48.0 years in the mechanical valve group (P = 0.17); the ratio of male to female patients was 3.2 in the Ross procedure group and 2.7 in the mechanical valve group (P = 0.46). Linearized all-cause mortality rate was 0.53% per patient-year in the Ross procedure group compared with 0.30% per patient-year in the mechanical valve group (matched hazard ratio, 1.86; 95% confidence interval, 0.58 to 5.91; P = 0.32). Late survival was comparable to that of the general German population.” (M. M. Mokhles, m.mokhles@erasmusmc.nl)

>>>PNN NewsWatch
* Lack of bipartisan support of health care reform is a chief regret of pharmacist Mark Hayes, a former Senate Finance staffer who was involved in the Gang of Six negotiations during the summer of 2009, Kaiser Health News reports.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Jan. 10, 2011 * Vol. 18, No. 6
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Jan. 8 issue of Lancet (2011; 377).
TB in Contacts of Patients with Resistant Infections: Tuberculosis is so common in people living with patients with multidrug-resistant (MDR) or extensively drug-resistant (XDR) cases that they should be routinely screened and when positive, treated for resistant bacteria until shown otherwise, a study concludes (pp. 147–52). Analyzed retrospectively in Peru for the 1996–2003 time period, 693 households with index patients with MDR tuberculosis showed the following: “In 48 households, the Mycobacterium tuberculosis isolate from the index patient was XDR. Of the 4,503 household contacts, 117 (2.60%) had active tuberculosis at the time the index patient began MDR tuberculosis treatment—there was no difference in prevalence between XDR and MDR tuberculosis households. During the 4-year follow-up, 242 contacts developed active tuberculosis—the frequency of active tuberculosis was nearly two times higher in contacts of patients with XDR tuberculosis than it was in contacts of patients with MDR tuberculosis (hazard ratio 1.88, 95% CI 1.10–3.21). In the 359 contacts with active tuberculosis, 142 (40%) had had isolates tested for resistance against first-line drugs, of whom 129 (90.9%, 95% CI 85.0–94.6) had MDR tuberculosis.” (M. C. Becerra, mbecerra@post.harvard.edu)
Editorialists add that infection-control measures may be needed in homes of patients with drug-resistant tuberculosis, including education on TB transmission, cough hygiene, and when possible, separate accommodations (
pp. 103–4): “In Peru, XDR patients were treated for tuberculosis before diagnosis with drug-resistant tuberculosis, for a median of almost 1 year longer than patients with MDR tuberculosis. Patients with XDR tuberculosis also took substantially longer to convert to negative sputum cultures, and had higher rates of treatment failure than did those with MDR tuberculosis. These findings suggest that in addition to an increased transmission risk before diagnosis and treatment initiation, XDR tuberculosis cases might also be associated with an increased transmission after treatment initiation. This increased risk after treatment is also likely to occur in any patients with drug-resistant tuberculosis who are slow to respond to treatment or in whom treatment does not work. Thus, the benefits of ambulatory treatment regarding increased capacity to provide treatment and improved outcomes might need to be balanced against the risk of ongoing transmission after treatment initiation.” (H. Cox, hcox@burnet.edu.au)

>>>BMJ Highlights
Source:
Early-release articles from BMJ (2011; 342).
Vaccines, Autism & Fraud: Commenting on the first of three investigative reports into the Wakefield paper linking vaccines with autism and published over a decade ago in Lancet (c5347; B. Deer; www.briandeer.com), the BMJ editor writes (d22): “Science is based on trust. Without trust, research cannot function and evidence based medicine becomes a folly. Journal editors, peer reviewers, readers, and critics have all based their responses to Wakefield’s small case series on the assumption that the facts had at least been honestly documented. Such a breach of trust is deeply shocking. And even though almost certainly rare on this scale, it raises important questions about how this could happen, what could have been done to uncover it earlier, what further inquiry is now needed, and what can be done to prevent something like this happening again.” (F. Godlee, fgodlee@bmj.com)

>>>PNN NewsWatch
* The U.S. Supreme Court will hear arguments in the Sorrell v. IMS case, the Washington Post reports. It involves a Vermont law prohibiting use of prescription drug records for marketing purposes. The law was struck down by the U.S. Court of Appeals for the 2nd Circuit on First Amendment grounds, but similar laws in other states have been upheld by the Court of Appeals for the 1st Circuit.

>>>PNN JournalWatch
* Gout Therapeutics: New Drugs for an Old Disease, in Lancet, 2011; 377: 165–77. (C. M. Burns, chris.burns@hitchcock.org)
* A Quality-Based Review of Randomized Controlled trials of Psychodynamic Psychotherapy, in
American Journal of Psychiatry, 2011; 168: 19–28. (A. J. Gerber)
* Recent Advances in Sarcoidosis, in
Chest, 2011; 139: 174–82. (A. S. Morgenthau, adam.morgenthau@mssm.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Jan. 11, 2011 * Vol. 18, No. 7
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release articles from and Jan. 10 issue of the Archives of Internal Medicine (2011; 171).
Therapeutic Complexity & Adherence to Cardiovascular Medications: Adherence to cardiovascular medications is 8% lower among patients whose refills for multiple medications cannot be obtained at the same time, according to a study of statins, ACE inhibitors, and ARBs in 2006–07 (doi: 10.1001/archinternmed.2010.495). The researchers looked at 1.8 million prescriptions for statins and 1.5 million ACEI/ARB prescriptions. Complexity was judged in the first 3 months after a patient’s initial prescription by the number of medications, prescribers, pharmacies, and pharmacy visits, along with refill consolidation (number of visits per fill). Results showed: “The statin cohort had a mean age of 63 years and were 49% male. On average, during the 3-month complexity assessment period, statin users filled 11.4 prescriptions for 6.3 different medications, had prescriptions written by 2 prescribers, and made 5.0 visits to the pharmacy. Results for ACEI/ARB users were similar. Greater prescribing and filling complexity was associated with lower levels of adherence. In adjusted models, patients with the least refill consolidation had adherence rates that were 8% lower over the subsequent year than patients with the greatest refill consolidation.” (N. K. Choudhry, nchoudhry@partners.org)
Having a “pharmacy home” could be a major element in addressing the problems uncovered in this study, editorialists add (
doi: 10.1001/archinternmed.2010.481): “Aiming to improve adherence, health care providers can encourage patients to simplify their pattern of filling medications by using a single pharmacy or synchronizing refill dates. Having a pharmacy home, as the authors propose, might also be helpful for maintaining an accurate medication list and avoiding drug–drug interactions. Though the present study does not provide direct evidence for these practices, their potential to improve adherence is intriguing.…
“This study provides a valuable step forward in measuring the complexities of prescription medication management and its effect on adherence. Based on the results of this study, additional research is needed to determine if a reduction in therapeutic complexity (ie, fewer prescribers and/or pharmacies or maximal refill consolidation) positively affects adherence. Few published adherence interventions have addressed complexity comprehensively. Such programs are most likely to benefit patients with multimorbidity and complex medication regimens.” (A. H. Kripalani,
sunil.kripalani@vanderbilt.edu)
Smoking Cessation Efforts in Hospitalized MI Patients: Smoking cessation counseling is projected to be a cost-effective intervention in patients hospitalized for acute myocardial infarction, researchers report (pp. 39–45). A Monte Carlo model was used to estimate health and economic outcomes for 327,600 smokers hospitalized for AMI, with these results: “Implementation of smoking cessation counseling with follow-up contact for the 2010 cohort of hospitalized smokers would create 50,230 new quitters, cost $27.3 million in nurse wages and materials, and prevent 1,380 nonfatal AMIs and 7,860 deaths. During a 10-year period, it would save $22.1 million in reduced hospitalizations but increase health care costs by $166.4 million, primarily through increased longevity. Productivity costs from premature death would fall by $1.99 billion and nonmedical expenditures would increase by $928 million, for a net positive value to society of $894 million. The program would cost $540 per quitter considering only intervention costs. Cost-effectiveness would be $5,050 per quality-adjusted life-year. Results were sensitive to the utility and incidence of nonfatal AMI and the potential effect of pharmacotherapies.” (J. A. Ladapo, jladapo@post.harvard.edu)

>>>PNN NewsWatch
* Fentanyl transmucosal tablets (Abstral, ProStraken) have been approved by FDA for managing breakthrough pain in adults with cancer who already use opioid pain medications around the clock and who need and are able to safely use high doses of an additional opioid medicine. Abstral is available only through a Risk Evaluation and Mitigation Strategy (REMS) program, which requires enrollment by pharmacies, distributors, and health care professionals who prescribe to outpatients.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Jan. 12, 2011 * Vol. 18, No. 8
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Jan. 12 issue of JAMA (2011; 305).
Herpes Zoster Vaccine in Older Adults: Herpes zoster is reduced among immunocompetent adults aged 60 or older who receive the vaccine, researchers report (pp. 160–6). A retrospective study of 75,761 vaccinees found these differences in comparison with 227,283 unvaccinated members of the Kaiser Permanente system in southern California: “Herpes zoster vaccine recipients were more likely to be white, women, with more outpatient visits, and fewer chronic diseases. The number of herpes zoster cases among vaccinated individuals was 828 in 130,415 person–years (6.4 per 1,000 person–years; 95% confidence interval [CI], 5.9–6.8), and for unvaccinated individuals it was 4,606 in 355,659 person–years (13.0 per 1,000 person–years; 95% CI, 12.6–13.3). In adjusted analysis, vaccination was associated with a reduced risk of herpes zoster (hazard ratio [HR], 0.45; 95% CI, 0.42–0.48); this reduction occurred in all age strata and among individuals with chronic diseases. Risk of herpes zoster differed by vaccination status to a greater magnitude than the risk of unrelated acute medical conditions, suggesting results for herpes zoster were not due to bias. Ophthalmic herpes zoster (HR, 0.37; 95% CI, 0.23–0.61) and hospitalizations coded as herpes zoster (HR, 0.35; 95% CI, 0.24–0.51) were less likely among vaccine recipients.” (H. F. Tseng, Hung-Fu.x.Tseng@kp.org)
Candesartan v. Losartan in Heart Failure: Candesartan produced lower mortality risk among Swedish patients with heart failure than losartan, a study shows (pp. 175–82). Both are ARBs, but candesartan has higher affinity for AT1 receptors. Investigators looked at a HF registry that contained outcomes data on 30,254 unique patients seen at Swedish hospitals and clinics between 2000 and 2009. Survival analyzed by the Kaplan–Meier method showed these results: “One-year survival was 90% (95% confidence interval [CI], 89%–91%) for patients receiving candesartan and 83% (95% CI, 81%–84%) for patients receiving losartan, and 5-year survival was 61% (95% CI, 54%–68%) and 44% (95% CI, 41%–48%), respectively (log-rank P < .001). In multivariate analysis with adjustment for propensity scores, the hazard ratio for mortality for losartan compared with candesartan was 1.43 (95% CI, 1.23–1.65; P < .001). The results persisted in stratified analyses.” (L. H. Lund, lars.lund@alumni.duke.edu)

>>>Infectious Disease Report
Source:
Feb. 1 issue of Clinical Infectious Diseases (2011; 52).
Guidelines for MRSA Infections: New guidelines for treatment of methicillin-resistant Staphylococcus aureus are provided by the Infectious Diseases Society of America (e18–e55): “The guidelines are intended for use by health care providers who care for adult and pediatric patients with MRSA infections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections, bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system infections. Recommendations are provided regarding vancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibility to vancomycin, and vancomycin treatment failures.” (C. Liu, catherine.liu@ucsf.edu)
Amoxicillin for Nonsevere Pneumonia: In a trial in infants and young children with nonsevere pneumonia, amoxicillin was no better than placebo (pp. 293–300). In 900 patients aged 2–59 months, treatment with 3 days of amoxicillin 45 mg/kg/d showed: “In per-protocol analysis at day 3, 31 (7.2%) of the 431 children in the amoxicillin arm and 37 (8.3%) of the 442 in placebo group had therapy failure. This difference was not statistically significant (odds ratio [OR], .85; 95%CI, .50–1.43; P = .60). The multivariate analysis identified history of difficult breathing (OR, 2.86; 95% CI, 1.29–7.23; P = .027) and temperature >37.5°C 100°F at presentation (OR, 1.99; 95% CI, 1.37–2.90; P = .0001) as risk factors for treatment failure by day 5.” (T. Hazir, tabishhazir@hotmail.com)

>>>PNN NewsWatch
* FDA is reviewing the clinical benefits of midodrine, the agency said yesterday. Data have not confirmed the effects the drug was expected to have when it was approved under accelerated procedures for treatment of symptomatic orthostatic hypertension, FDA said.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Jan. 13, 2011 * Vol. 18, No. 9
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 13 issue of the New England Journal of Medicine (2011; 364).
Treatment of Acute Otitis Media: Two research studies and an editorial compare “watchful waiting” with antibiotic therapy for acute otitis media in pediatrics.
Time to symptom resolution and symptom burden of acute otitis media were significantly reduced among 291 patients ages 6–23 months when they received amoxicillin–clavulanate for 10 days, a study shows, compared with placebo (
pp. 105–15): “Among the children who received amoxicillin–clavulanate, 35% had initial resolution of symptoms by day 2, 61% by day 4, and 80% by day 7; among children who received placebo, 28% had initial resolution of symptoms by day 2, 54% by day 4, and 74% by day 7 (P = 0.14 for the overall comparison). For sustained resolution of symptoms, the corresponding values were 20%, 41%, and 67% with amoxicillin–clavulanate, as compared with 14%, 36%, and 53% with placebo (P = 0.04 for the overall comparison). Mean symptom scores over the first 7 days were lower for the children treated with amoxicillin–clavulanate than for those who received placebo (P = 0.02). The rate of clinical failure—defined as the persistence of signs of acute infection on otoscopic examination—was also lower among the children treated with amoxicillin–clavulanate than among those who received placebo: 4% versus 23% at or before the visit on day 4 or 5 (P < 0.001) and 16% versus 51% at or before the visit on day 10 to 12 (P < 0.001). Mastoiditis developed in one child who received placebo. Diarrhea and diaper-area dermatitis were more common among children who received amoxicillin–clavulanate. There were no significant changes in either group in the rates of nasopharyngeal colonization with nonsusceptible Streptococcus pneumoniae.” (A. Hoberman, hoberman@chp.edu)
Amoxicillin–clavulanate was also beneficial in a second trial, this one of 319 children ages 6–35 months with acute otitis media and providing 7 days of treatment, but adverse effects were noted in those on antibiotics (
pp. 116–26): “Treatment failure occurred in 18.6% of the children who received amoxicillin–clavulanate, as compared with 44.9% of the children who received placebo (P < 0.001). The difference between the groups was already apparent at the first scheduled visit (day 3), at which time 13.7% of the children who received amoxicillin–clavulanate, as compared with 25.3% of those who received placebo, had treatment failure. Overall, amoxicillin–clavulanate reduced the progression to treatment failure by 62% (hazard ratio, 0.38; 95% confidence interval [CI], 0.25 to 0.59; P < 0.001) and the need for rescue treatment by 81% (6.8% vs. 33.5%; hazard ratio, 0.19; 95% CI, 0.10 to 0.36; P < 0.001). Analgesic or antipyretic agents were given to 84.2% and 85.9% of the children in the amoxicillin–clavulanate and placebo groups, respectively. Adverse events were significantly more common in the amoxicillin–clavulanate group than in the placebo group. A total of 47.8% of the children in the amoxicillin–clavulanate group had diarrhea, as compared with 26.6% in the placebo group (P < 0.001); 8.7% and 3.2% of the children in the respective groups had eczema (P = 0.04).” (A. Ruohola, aino.ruohola@utu.fi)
Complimenting these researchers for providing studies with appropriate designs and meticulous assessments, an editorialist writes (
pp. 168–9): “The results of each study showed a significant benefit among children who received the drug with respect to the duration of acute signs of illness. Among children with moderate disease and children with severe disease, the rates of clinical failure were higher in the placebo group than in the amoxicillin–clavulanate group. As expected, the condition of many children in the placebo group improved without antibiotics, and more children in the antibiotic groups had associated side effects. Since the physician cannot determine at the onset of the illness which child is likely to benefit from antimicrobial therapy, we need to consider these data as applicable to all young children in whom a certain diagnosis of acute otitis media has been made. Is acute otitis media a treatable disease? The investigators in Pittsburgh and Turku have provided the best data yet to answer the question, and the answer is yes; more young children with a certain diagnosis of acute otitis media recover more quickly when they are treated with an appropriate antimicrobial agent.” (J. O. Klein)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Jan. 13, 2011 * Special alert
Providing news and information about medications and their proper use

Over the next 3 years, the amount of acetaminophen in each tablet or capsule of prescription combination products must be reduced to no more than 325 mg, FDA announced this morning. The agency also said that companies must add liver toxicity warnings to these products. Nonprescription products are not affected by this action.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Jan. 14, 2011 * Vol. 18, No. 10
Providing news and information about medications and their proper use

>>>Diabetes Report
Source:
Jan. issue of Diabetes Care (2011; 34).
Pharmacists & Blood Pressure Control: Adding pharmacists to primary care teams significantly improved blood pressure control among 260 patients at clinics in Edmonton, Canada, researchers report (pp. 20–6). In a randomized controlled trial with blinded determination of outcomes, pharmacists performed medication and physical assessments, took histories, and managed medications using “guideline-concordant recommendations.” Compared with usual care, pharmacist-managed care showed these effects based on a primary outcome of a decrease in systolic blood pressure at 1 year of 10% or more: “57% were women, the mean age was 59 years, diabetes duration was 6 years, and blood pressure was 129/74 mmHg. Forty-eight of 131 (37%) intervention patients and 30 of 129 (23%) control patients achieved the primary outcome (odds ratio 1.9 [95% CI 1.1–3.3]; P = 0.02). Among 153 patients with inadequately controlled hypertension at baseline, intervention patients (n = 82) were significantly more likely than control patients (n = 71) to achieve the primary outcome (41 [50%] vs. 20 [28%]; 2.6 [1.3–5.0]; P = 0.007) and recommended blood pressure targets (44 [54%] vs. 21 [30%]; 2.8 [1.4–5.4]; P = 0.003). The 10-year risk of cardiovascular disease, based on changes to the UK Prospective Diabetes Study Risk Engine, were predicted to decrease by 3% for intervention patients and 1% for control patients (P = 0.005).” (S. H. Simpson, ssimpson@pharmacy.ualberta.ca)
Vitamins & Diabetes Risk: In the National Institutes of Health–American Association of Retired Persons Diet and Health Study, frequent users of vitamin C and calcium supplements had significantly lower diabetes risk, but multivitamin use had no effect (pp. 108–14). Food-frequency questionnaires in 1995–96 and diabetes diagnoses after 2000 showed: “Compared with nonusers of any multivitamins, the multivariate ORs among users were 1.07 (95% CI 0.94–1.21) for taking vitamins less than once per week, 0.97 (0.88–1.06) for one to three times per week, 0.92 (0.84–1.00) for four to six times per week, and 1.02 (0.98–1.06) for seven or more times per week (P for trend = 0.64). Significantly lower risk of diabetes was associated with the use of vitamin C or calcium supplements. The multivariate ORs comparing daily users with nonusers were 0.91 (0.86–0.97) for vitamin C supplements and 0.85 (0.80–0.90) for calcium supplements.” (H. Chen, chenh2@niehs.nih.gov)

>>>Cardiology Highlights
Source:
Jan. 18 issue of the Journal of the American College of Cardiology (2011; 57).
Reducing Racial Disparities in Cardiovascular Care: A white paper describes “the rationale for the American College of Cardiology’s Coalition to Reduce Racial and Ethnic Disparities in Cardiovascular Disease Outcomes (credo) and the tools that will be made available to cardiologists and others treating cardiovascular disease (CVD) to better meet the needs of their diverse patient populations” (pp. 245–52): “Even as the patient population with CVD grows increasingly diverse in terms of race, ethnicity, age, and sex, many cardiologists and other health care providers are unaware of the negative influence of disparate care on CVD outcomes and do not have the tools needed to improve care and outcomes for patients from different demographic and socioeconomic backgrounds. Reviewed published reports assessed the need for redressing CVD disparities and the evidence concerning interventions that can assist cardiology care providers in improving care and outcomes for diverse CVD patient populations. Evidence points to the effectiveness of performance measure-based quality improvement, provider cultural competency training, team-based care, and patient education as strategies to promote the elimination of disparate CVD care and in turn might lead to better outcomes. credo has launched several initiatives built on these evidence-based principles and will be expanding these tools along with research. credo will provide the CVD treatment community with greater awareness of disparities and tools to help close the gap in care and outcomes for all patient subpopulations.” (L. L. Hall, lhall@acc.org)

>>>PNN NewsWatch
* Details on yesterday’s FDA action regarding acetaminophen in prescription combination products are available on the agency’s website.
*
PNN will not be published on Mon., Jan. 17, King Day.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Jan. 18, 2011 * Vol. 18, No. 11
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Early-release article from BMJ (2011; 342).
Cardiovascular Safety of NSAIDs: Cardiovascular safety should be a concern with use of any NSAID—even the safest one, naproxen—a network meta-analysis concludes (c7086). Using data from the literature and conferences, FDA, manufacturers, and bibliographic databases, the investigators determined: “31 trials in 116,429 patients with more than 115,000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death.” (P. Jüni, juni@ispm.unibe.ch)

>>>Internal Medicine Report
Source:
Early-release article from the Annals of Internal Medicine (2011; 154).
Osteoporosis Screening: In an update to 2002 guidelines, the U.S. Preventive Services Task Force “recommends screening for osteoporosis in women aged 65 years or older and in younger women whose fracture risk is equal to or greater than that of a 65-year-old white woman who has no additional risk factors” (early release). “The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis in men,” the guidelines note, adding: “Evidence of the effectiveness of treatment of osteoporosis in men is limited. There are no primary prevention trials of bisphosphonates in men and only 2 secondary prevention trials of alendronate. When the 2 trials were pooled, alendronate was associated with a reduced risk for vertebral fractures (odds ratio [OR], 0.35 [CI, 0.17 to 0.77]), and the effect on nonvertebral fractures was not statistically significant (OR, 0.73 [CI, 0.32 to 1.67]). A single primary prevention trial of parathyroid hormone reported a non–statistically significant trend toward a reduction in vertebral and nonvertebral fractures. None of the other therapies for osteoporosis in men has been evaluated in randomized trials.” (U.S. Preventive Services Task Force, www.preventiveservices.ahrq.gov)

>>>Lancet Highlights
Source:
Jan. 15 issue of Lancet (2011; 377).
Vitamin D & TB: Use of four doses of vitamin D3 showed no significant effects on pulmonary tuberculosis in 146 patients, but those with a recessive genotype of the TakI gene had faster conversions of sputum cultures, a study shows (pp. 242–50). Patients in the vitamin D3 group received 2.5 mg of the nutrient on days 0, 14, 28, and 42 of standard tuberculosis treatment, with these results: “Median time to sputum culture conversion was 36.0 days in the intervention group and 43.5 days in the placebo group (adjusted hazard ratio 1.39, 95% CI 0.90–2.16; p = 0.14). TakI genotype modified the effect of vitamin D supplementation on time to sputum culture conversion (pinteraction = 0.03), with enhanced response seen only in patients with the tt genotype (8.09, 95% CI 1.36–48.01; p = 0.02). FokI genotype did not modify the effect of vitamin D supplementation (pinteraction = 0.85). Mean serum 25-hydroxyvitamin D concentration at 56 days was 101.4 nmol/L in the intervention group and 22.8 nmol/L in the placebo group (95% CI for difference 68.6–88.2; p < 0.0001).” (A. R. Martineau, a.martineau@qmul.ac.uk)

>>>PNN NewsWatch
* Rare but severe liver injury can occur with dronedarone (Multaq, Sanofi-Aventis), FDA said on Friday.

>>>PNN JournalWatch
* Culturally Appropriate Storytelling to Improve Blood Pressure, in Annals of Internal Medicine, 2011; 154: 77–84. (T. K. Houston, Thomas.Houston@umassmed.edu)
* Exogenous and Endogenous Glucocorticoids in Rheumatic Diseases, in
Arthritis & Rheumatism, 2011; 63: 1–9. (F. Buttgereit, frank.buttgereit@charite.de)
* Taming Glioblastoma by Targeting Angiogenesis: 3 Years Later [editorial], in
Journal of Clinical Oncology, 2011; 29: 124–6. (E. T. Wong)
* Probiotics, Enteric and Diarrheal Diseases, and Global Health, in
Gastroenterology, 2011; 140: 8–14.e9. (J. Versalovic, jamesv@bcm.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Jan. 19, 2011 * Vol. 18, No. 12
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Jan. 19 issue of JAMA (2011; 305).
Escitalopram for Hot Flashes: The SSRI escitalopram reduced the number and severity of menopausal hot flashes among 205 healthy women treated for 8 weeks, researchers report (pp. 267–74). Compared with placebo, escitalopram produced these results based on prospective daily diaries at weeks 4 and 8: “Mean (SD) daily hot flash frequency was 9.78 (5.60) at baseline. In a modified intent-to-treat analysis that included all randomized participants who provided hot flash diary data, the mean difference in hot flash frequency reduction was 1.41 (95% CI, 0.13-2.69) fewer hot flashes per day at week 8 among women taking escitalopram (P < .001), with mean reductions of 4.60 (95% CI, 3.74–5.47) and 3.20 (95% CI, 2.24–4.15) hot flashes per day in the escitalopram and placebo groups, respectively. Fifty-five percent of women in the escitalopram group vs 36% in the placebo group reported a decrease of at least 50% in hot flash frequency (P = .009) at the 8-week follow-up. Reductions in hot flash severity scores were significantly greater in the escitalopram group (−0.52; 95% CI, −0.64 to −0.40 vs −0.30; 95% CI, −0.42 to −0.17 for placebo; P < .001). Race did not significantly modify the treatment effect (P = .62). Overall discontinuation due to adverse events was 4% (7 in the active group, 2 in the placebo group). Three weeks after treatment ended, women in the escitalopram group reported a mean 1.59 (95% CI, 0.55–2.63; P = .02) more hot flashes per day than women in the placebo group.” (E. W. Freeman, freemane@mail.med.upenn.edu)
Beta-Amyloid & Cognitive Decline: Commenting on a study showing that lower levels of plasma beta-amyloid were associated with decreased rates of cognitive decline among elderly patients without dementia (pp. 261–6; K. Yaffe, kristine.yaffe@ucsf.edu), an editorialist writes about “mapping out biomarkers for Alzheimer disease” (pp. 304–5): “With biomarker research coming of age, it is time that the research methods for the evaluation of biomarkers become as stringent as, for example, the evaluation of new treatments. The stakes involved in finding good biomarkers for AD and other neurodegenerative diseases are high indeed—too high to be able to afford jumping to unwarranted conclusions and heading in wrong directions. Only through future studies using rigorous study designs can the role of either florbetapir-PET imaging or plasma beta-amyloid 42/40 in diagnosis or prediction of AD be determined.” (M. M. B. Breteler, m.breteler@erasmusmc.nl)
A Socratic Impact Factor: A physician, writing in the Piece of My Mind column, shares his joy when a former resident recalls the writer teaching him how to use a tongue blade to amplify the precordial impulse, and then adds (p. 230): “Journals are often judged by their impact factor, ie, the number of times articles are cited over a set period of time. The impact factor I’m describing is less quantitative but no less important. Institutions, if they’re fortunate, have at least one physician with a large impact factor, a physician–educator who inspires learners to inspire others. Our hospital has several but, in my life, one in particular has impacted me time and again. Clad in his trademark plaid pants, he taught me how to talk with patients. At the bedside, he taught me to appreciate the subtleties of the second heart sound and the jugular veins. In the hallway, he taught me that being nice isn’t always the best way to advocate for one’s patients against the powers-that-be (this from the nicest physician I know). He showed me and many other learners how to observe, how to act, and how to interact. We in turn have imparted these teachings to subsequent learners. Thus, Dr Plaid Pants has a huge impact factor that extends over time to students here, there, and everywhere.” (R. E. Hirschtick, rober@northwestern.edu)

>>>PNN NewsWatch
* Spinosad (Natroba Topical Suspension, ParaPRO) 0.9% has been approved by FDA for treatment of head lice infestation in patients ages 4 years or older. In two randomized, controlled studies, 552 participants received a 10-minute treatment with spinosad. A second treatment was applied if lice were seen a week later. Approximately 86% of patients were lice-free 14 days later, compared with 44% of 486 control group patients treated with permethrin 1%. Common adverse events reported with spinosad included redness or irritation of the eyes and skin.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Jan. 20, 2011 * Vol. 18, No. 13
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 20 issue of the New England Journal of Medicine (2011; 364).
Iniparib in Metastatic Triple-Negative Breast Cancer: Added to chemotherapy in a study of 123 patients with metastatic triple-negative breast cancer, iniparib improved outcomes without toxic effects, researchers report (pp. 205–14). Tumor cells are termed triple negative in breast cancer when they are negative for the estrogen and progesterone receptors and they do not overexpress human epidermal growth factor receptor type 2. In the study, gemcitabine and carboplatin were administered with or without iniparib, a small molecule that inhibits poly(adenosine diphosphate–ribose) polymerase (PARP). With clinical benefit defined as the rate of objective (complete or partial) response plus the rate of stable disease for 6 months or more, results showed: “The addition of iniparib to gemcitabine and carboplatin improved the rate of clinical benefit from 34% to 56% (P = 0.01) and the rate of overall response from 32% to 52% (P = 0.02). The addition of iniparib also prolonged the median progression-free survival from 3.6 months to 5.9 months (hazard ratio for progression, 0.59; P = 0.01) and the median overall survival from 7.7 months to 12.3 months (hazard ratio for death, 0.57; P = 0.01). The most frequent grade 3 or 4 adverse events in either treatment group included neutropenia, thrombocytopenia, anemia, fatigue or asthenia, leukopenia, and increased alanine aminotransferase level. No significant difference was seen between the two groups in the rate of adverse events.” (J. O’Shaughnessy, joyce.oshaughnessy@usoncology.com)
If these Phase II results are confirmed in larger Phase III trials, PARP inhibition could become “a rational approach to treating triple-negative breast cancer and the first therapy showing a survival advantage over chemotherapy alone,” an editorialist writes (
pp. 277–9). Still, important questions would remain, especially with regard to patients’ BRCA genotype: “First, does the activity of iniparib in this trial result from PARP inhibition or an unknown mechanism? More generally, since the ‘BRCAness’ of triple-negative breast cancers is not proved, do PARP inhibitors as a class have activity in cancers lacking BRCA1 or BRCA2 dysfunction? Can PARP inhibition augment DNA-damaging chemotherapy administered to other subtypes of breast cancer or other types of tumor? Which DNA-damaging chemotherapy best synergizes with PARP inhibitors? Adjuvant trials of PARP inhibitors for patients with early-stage breast cancer, in which these drugs will be added to chemotherapy delivered with a curative intent, are already being developed. The many roles of PARPs outside of DNA repair raise concern that PARP inhibitors may exhibit as-yet unknown ‘on-target’ toxic effects, such as the diet-induced obesity and insulin resistance seen in PARP1-deficient mouse models. In addition, the risk of secondary cancer from DNA-repair inhibition needs to be considered carefully if these agents are used for longer periods in healthier patients.” (L. A. Carey)
Constitutionality of Health Care Insurance Mandate: The constitutionality of the Affordable Care Act is examined in a Perspective article that concludes, “The federal government has never exercised its authority in this manner before—and that’s what makes answering the constitutional question so hard.” (pp. 201–3). The law, which the House of Representatives voted to repeal yesterday, faces a more serious challenge in federal courts, where its requirement that Americans buy health insurance from private industry is at issue: “Much of the commentary on the ACA cases reflects political attitudes toward the role of government in health care delivery and financing. Those who believe that the federal government must play a central role tend to believe that the ACA must be constitutional; those who think that the government should have little or no role believe the law must be unconstitutional. But the hard question for the Court will not be the appropriate role of the government in health care. It is a much more general question of constitutional interpretation: Does the Commerce Clause authorize Congress to require individuals to buy products the Congress thinks they should buy to further the general welfare? That question is at the core of our constitutional democracy.” (W. K. Mariner)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Jan. 21, 2011 * Vol. 18, No. 14
Providing news and information about medications and their proper use

>>>Oncology Highlights
Source:
Jan. issue of the Journal of Clinical Oncology (2011; 29).
Suncreens & Melanoma: Regular use of sunscreen cuts down on risk of melanoma, according to a longitudinal study from Australia (pp. 257–63). Residents of a township who participated in a beta-carotene study from 1992 to 1996 were assigned to daily or discretionary sunscreen use. Followed through 2006, the participants had these outcomes with respect to melanoma occurrence: “Ten years after trial cessation, 11 new primary melanomas had been identified in the daily sunscreen group, and 22 had been identified in the discretionary group, which represented a reduction of the observed rate in those randomly assigned to daily sunscreen use (hazard ratio [HR], 0.50; 95% CI, 0.24 to 1.02; P = .051). The reduction in invasive melanomas was substantial (n = 3 in active v 11 in control group; HR, 0.27; 95% CI, 0.08 to 0.97) compared with that for preinvasive melanomas (HR, 0.73; 95% CI, 0.29 to 1.81).” (A. Green, adele.green@qimr.edu.au)
After noting that sunscreen use by the general population is suboptimal, an editorialist writes (
pp. 249–50): “Sunscreen use alone will likely not reduce the incidence of skin cancer, which is an increasingly widespread and serious public health problem in the United States and globally. In addition to sunscreen use, excess exposure to ultraviolet rays should be avoided, clothing should be used to shield skin from the sun, and sun-safe environments should be used for outdoor recreation. In addition, sunscreen use should be paired with regular self-examination of the skin. The question of its efficacy with respect to melanoma prevention should no longer deter scientists or clinicians from recommending sunscreen use.” (P. A. Gimotty)

>>>Allergy/Immunology Report
Source:
Jan. issue of the Journal of Allergy and Clinical Immunology (2011; 127).
Influenza Vaccine & Asthma: Patients with asthma benefited from vaccination against the pandemic H1N1 influenza virus that circulated in 2009–10, a study shows, but patients older than 60 with severe asthma might have needed twice the usual dose of antigen in the commercially available products (pp. 130–7.e3). The open-label trial, conducted in fall 2009, included 390 participants ages 12 to 79 years and showed the following: “In patients with mild-to-moderate asthma (n = 217), the 2009 H1N1 vaccine provided equal seroprotection 21 days after the first immunization at the 15-µg (90.6%; 95% CI, 83.5% to 95.4%) and 30-µg (95.3%; 95% CI, 89.4% to 98.5%) doses. In patients with severe asthma (n = 173), seroprotection 21 days after the first immunization was 77.9% (95% CI, 67.7% to 86.1%) and 94.1% (95% CI, 86.8% to 98.1%) at the 15- and 30-µg doses, respectively (P = .004). The second vaccination did not provide further increases in seroprotection. Participants with severe asthma who are older than 60 years showed the lowest seroprotection (44.4% at day 21) with the 15-µg dose but had adequate seroprotection with 30 µg. The 2 dose groups did not differ in seroconversion rates. There were no safety concerns.” (W. W. Busse, wwb@medicine.wisc.edu)
Advances in Pediatric Asthma: During 2010, pediatric asthma management improved through “steps to better understand the natural history of asthma, individualize asthma care, reduce asthma exacerbations, and manage inner-city asthma and some potential new ways to use available medications to improve asthma control,” according to an annual update (pp. 102–15; S. J. Szefler, szeflers@njhealth.org)

>>>PNN NewsWatch
* An uptick in cases of febrile seizures has been detected among infants and children younger than 2 years who received the 2010–11 Fluzone formulation of trivalent influenza vaccine, FDA and CDC reported yesterday. Fluzone is the only product licensed for use in this age group, and the federal recommendations for immunization of all persons 6 months and older have not changed based these Vaccine Adverse Event Reporting System (VAERS) data. The agencies noted in a Web posting that 4% of children have at least one febrile seizure sometime during their lives, usually between 6 months and 5 years of age, and that the peak incidence is at 14–18 months. FDA and CDC added that they are further analyzing VAERS data and will work with the manufacturer, Sanofi Pasteur, on any needed responses.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Jan. 24, 2011 * Vol. 18, No. 15
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Jan. 22 issue of Lancet (2011; 377).
Aliskiren & Amlodipine as Initial Therapy in Hypertension: The combination of aliskiren and amlodipine can be recommended for initial treatment of hypertension, according to authors of a Novartis-funded trial conducted in 10 countries (pp. 312–20). Participants had initial systolic blood pressures of 150–180 mm Hg, and they were assigned in 1:1:2 proportions to receive aliskiren 150 mg, amlodipine 5 mg, or the combination of the two drugs in those doses for 16 weeks. After that, all participants received combination therapy with twice the initial dose of each drug, with these results: “315 patients initially allocated to aliskiren, 315 allocated to amlodipine, and 617 allocated to aliskiren plus amlodipine were available for analysis. Patients given initial combination therapy had a 6.5 mm Hg (95% CI 5.3 to 7.7) greater reduction in mean systolic blood pressure than the monotherapy groups (p < 0.0001). At 24 weeks, when all patients were on combination treatment, the difference was 1.4 mm Hg (95% CI –0.05 to 2.9; p = 0.059). Adverse events caused withdrawal of 85 patients (14%) from the initial aliskiren plus amlodipine group, 45 (14%) from the aliskiren group, and 58 (18%) from the amlodipine group. Adverse events were peripheral oedema, hypotension, or orthostatic hypotension.” (M. J. Brown, m.j.brown@cai.cam.ac.uk)
Exemestane in Early Breast Cancer: For postmenopausal women with hormone-receptor–positive early breast cancer, exemestane alone or following tamoxifen “might be judged to be appropriate options,” conclude investigators from the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial (pp. 321–31). Conducted in hospitals in nine countries, the study included nearly 10,000 women ages 35–96. They received open-label exemestane 25 mg/day alone or following tamoxifen 20 mg/day for 5 years, with these results: “4,154 (85%) patients in the sequential group and 4,186 (86%) in the exemestane alone group were disease free at 5 years (hazard ratio 0.97, 95% CI 0.88–1.08; p = 0.60). In the safety analysis, sequential treatment was associated with a higher incidence of gynaecological symptoms (942 [20%] of 4,814 vs 523 [11%] of 4,852), venous thrombosis (99 [2%] vs 47 [1%]), and endometrial abnormalities (191 [4%] vs 19 [<1%]) than was exemestane alone. Musculoskeletal adverse events (2,448 [50%] vs 2,133 [44%]), hypertension (303 [6%] vs 219 [5%]), and hyperlipidaemia (230 [5%] vs 136 [3%]) were reported more frequently with exemestane alone.” (C. J. H. van de Velde, c.j.h.van_de_velde@lumc.nl)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2011; 342).
Cholesterol Levels as Indicators of Statin Adherence: Failure of patients’ LDL or total cholesterol to fall during statin therapy can be used as one indicator of nonadherence, a study shows (d12). Among 9,014 patients with coronary heart disease, about one-half of nonadherent patients had a rise in LDL cholesterol during the first year after pravastatin was started, while only 6% of adherent patients did so. “A patient with no change in low density lipoprotein cholesterol concentration has a post-test probability of being completely non-adherent of between 67% and 95% and a post-test probability of being partially non-adherent of between 48% and 89%,” the authors noted. (A. Hayen, andrew.hayen@sydney.edu.au)

>>>PNN NewsWatch
* Vilazodone (Viibryd, Clinical Data) has been approved by FDA for treatment of major depressive disorder. Expected in pharmacies in the second quarter of this year, the drug has an incompletely understood mechanism of action, but it is unique in that it selectively inhibits serotonin reuptake and is a partial agonist of serotonergic 5-HT1A receptors. In 8-week efficacy trials, the drug improved depressive symptoms. Adverse reactions most commonly included diarrhea (28%), nausea (23%), insomnia (6%), and vomiting (5%). Sexual dysfunction was reported by 2–4% of patients taking the drug.

>>>PNN JournalWatch
* Use of Non-steroidal Anti-inflammatory Drugs and Risk of Parkinson’s Disease: Nested Case–Control Study, in BMJ, 2011; 342: d198. (J A Driver, jdriver@partners.org)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Jan. 25, 2011 * Vol. 18, No. 16
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release articles from and Jan. 24 issue of the Archives of Internal Medicine (2011; 171).
Electronic Health Records & Quality: No clear improvement in quality of health care is associated with implementation of electronic health records (EHRs) and clinical decision support (CDS) systems, according to survey data on 255,402 ambulatory patient visits (doi: 10.1001/archinternmed.2010.527). Researchers looked at the 2005–07 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, looking for changes in 20 previously developed quality indicators. Results showed: “Electronic health records were used in 30% of an estimated 1.1 billion annual US patient visits. Clinical decision support was present in 57% of these EHR visits (17% of all visits). The use of EHRs and CDS was more likely in the West and in multiphysician settings than in solo practices. In only 1 of 20 indicators was quality greater in EHR visits than in non-EHR visits (diet counseling in high-risk adults, adjusted odds ratio, 1.65; 95% confidence interval, 1.21–2.26). Among the EHR visits, only 1 of 20 quality indicators showed significantly better performance in visits with CDS compared with EHR visits without CDS (lack of routine electrocardiographic ordering in low-risk patients, adjusted odds ratio, 2.88; 95% confidence interval, 1.69–4.90). There were no other significant quality differences.” (M. J. Romano, mromano4@jhmi.edu)
Editorialists write that one big problem with EHRs is the quality of information coming from “upstream data producers” (
doi: 10.1001/archinternmed.2010.518): “The Clean Water Act puts the responsibility on the upstream producers of impure water to clean it up. It does not make economic sense for each of the downstream users to do the cleanup work before they can use the water. The same principle should apply to health care data. The upstream data producers should deliver clean data that can be imported into downstream EHRs without additional work or cost.… Although many large national laboratories do offer electronic reports that follow such format and code standards, most diagnostic services, hospitals, dictation services, and other clinical data sources do not, because the current national incentives to automate and standardize medical data apply to the downstream EHRs, not to the systems that feed them. This has to change. Office practices and the medical societies that represent them have to demand clean, well-standardized data feeds for their EHRs, and policymakers need to support this requirement. Only when EHRs carry rich repositories can we expect EHRs to reach their promise and CDS to have measurable effects on a broad range of quality measures at the national level.” (C. McDonald, clement.mcdonald@nih.gov)
Influenza Risk in Hospitals: Person-to-person transmission of influenza virus in acute care settings increases patients’ risk of developing hospital-acquired influenza-like illness (HA-ILI), a study shows (pp. 151–7). During three community epidemics of influenza in the mid-2000s, relative risk (RR) data were prospectively recorded for 21,519 patients and 2,153 health care workers (HCWs): “For patients exposed to at least 1 contagious HCW compared with those with no documented exposure in the hospital, the RR of HA-ILI was 5.48 (95% confidence interval [CI], 2.09–14.37); for patients exposed to at least 1 contagious patient, the RR was 17.96 (95% CI, 10.07–32.03); and for patients exposed to at least 1 contagious patient and 1 contagious HCW, the RR was 34.75 (95% CI, 17.70–68.25).” (P. Vanhems, philippe.vanhems@chu-lyon.fr)
Ethnic Disparities in Immunization Rates: Cultural and linguistic barriers remain in provision of immunizations to patients of Hispanic descent, according to a study that assessed data from 244,618 Medicare beneficiaries (pp. 158–65). While 76% of non-Hispanic whites were immunized against influenza, the rates were significantly lower for Spanish- and English-speaking Hispanic patients (64% and 68%, respectively). Pneumococcal rates were also lower among Hispanics, but disparities were “consistently smaller” for those in managed care plans. (M. N. Elliott, elliott@rand.org)

>>>PNN NewsWatch
* “Process Validation: General Principles and Practices,” FDA’s guidance for manufacturers regarding quality risk management, is published in today’s Federal Register.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Jan. 26, 2011 * Vol. 18, No. 17
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Early-release article from and Jan. 26 issue of JAMA (2011; 305).
Care in Stroke Centers: Patients with acute ischemic strokes seen in designated stroke centers in New York State had a “modestly lower” risk of mortality and more frequently received thrombolytic therapy, researchers report (pp. 373–80). Data on 30,947 patients with stroke, 39,409 individuals with gastrointestinal hemorrhage, and 40,024 people with acute myocardial infarction were analyzed, with the latter two groups used to see if results were specific to stroke. Mortality over the first year following the index hospitalization showed these patterns: “Among 30,947 patients with acute ischemic stroke, 15,297 (49.4%) were admitted to designated stroke centers. Using the instrumental variable analysis, admission to designated stroke centers was associated with lower 30-day all-cause mortality (10.1% vs 12.5%; adjusted mortality difference, −2.5%; 95% confidence interval [CI], −3.6% to −1.4%; P < .001) and greater use of thrombolytic therapy (4.8% vs 1.7%; adjusted difference, 2.2%; 95% CI, 1.6% to 2.8%; P < .001). Differences in mortality also were observed at 1-day, 7-day, and 1-year follow-up. The outcome differences were specific for stroke, as stroke centers and nondesignated hospitals had similar 30-day all-cause mortality rates among those with gastrointestinal hemorrhage (5.0% vs 5.8%; adjusted mortality difference, +0.3%; 95% CI, −0.5% to 1.0%; P = .50) or acute myocardial infarction (10.5% vs 12.7%; adjusted mortality difference, +0.1%; 95% CI, −0.9% to 1.1%; P = .83).” (Y. Xian, ying.xian@duke.edu)
Seeking to prevent “death one stroke at a time,” an editorialist writes that comprehensive stroke centers (CSCs) are making a difference (
pp. 408–9): “What does the future hold for acute stroke care? A multitiered system of stroke care is developing, with the CSC at the top of the pyramid, the PSC in the middle, and the acute stroke ready hospital (ASRH) at the base. Within a geographical region, a small number of CSCs would provide care for patients with the most complicated stroke cases; a larger number of PSCs would provide care for the patients with typical, uncomplicated cases; and the ASRH would provide initial screening and triage and begin acute care for patients in a rural, small urban, or suburban setting. Emergency medical services personnel would perform initial screening and triage and would transport patients with a clearly defined stroke to the closest stroke center facility. Using telemedicine technologies, hospital personnel could communicate and transfer patients to the facility with the most appropriate level of care. Many states and guidelines now support and even mandate the diversion of patients suspected of having a stroke to the nearest stroke center facility.” (M. J. Alberts, m-alberts@northwestern.edu)
CER Needs Interdisciplinary Teams: Comparative effectiveness research (CER) and other new research methods will present challenges in real-world settings, write the authors of a Commentary who propose this solution (pp. 400–1): “One approach might be to broaden the Clinical and Translational Science Awards model of interdisciplinary research to focus on context-sensitive implementation research in diverse settings, both to develop new evidence regarding the effectiveness of high-priority CER interventions (eg, the use of patient navigators and care coordinators, medical home models, and strategies to reduce disparities) and translate the resulting evidence into practice. These research and field-testing units, which could be called interdisciplinary implementation and CER centers would include an interdisciplinary faculty capable of designing and executing multimodal implementation and evaluation research, as well as ready-to-roll field-testing sites and populations. They could leverage existing research networks, such as pediatric research in the office setting, to get as close as possible to the point of care. They would provide valuable inputs for comprehensive evidence sources, such as the Cochrane Effective Practice and Organization of Care Group, and serve as a framework in evaluating initiatives launched by the new Center for Medicare and Medicaid Innovation.” (P. Sullivan, paul.sullivan@srft.nhs.uk)
Safety of Energy Drinks: The high levels of caffeine in energy drinks, and their use in combination with alcohol, pose safety risks for users, Commentary authors write (doi: 10.1001/jama.2011.109; A. M. Arria, aarria@umd.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Jan. 27, 2011 * Vol. 18, No. 18
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 27 issue of the New England Journal of Medicine (2011; 364).
TPA in Dialysis Catheters: Used as a locking solution in central venous hemodialysis catheters, once-weekly recombinant tissue plasminogen activator reduced the frequency of catheter malfunction and bacteremia, compared with heparin, researchers report (pp. 303–12). In 225 patients on long-term hemodialysis, heparin 5000 units/mL three times per week and rt-PA 1 mg in each lumen at midweek gave these results in the Roche-sponsored study: “A catheter malfunction occurred in 40 of the 115 patients assigned to heparin only (34.8%) and 22 of the 110 patients assigned to rt-PA (20.0%)—an increase in the risk of catheter malfunction by a factor of almost 2 among patients treated with heparin only as compared with those treated with rt-PA once weekly (hazard ratio, 1.91; 95% confidence interval [CI], 1.13 to 3.22; P = 0.02). Catheter-related bacteremia occurred in 15 patients (13.0%) assigned to heparin only, as compared with 5 (4.5%) assigned to rt-PA (corresponding to 1.37 and 0.40 episodes per 1000 patient-days in the heparin and rt-PA groups, respectively; P = 0.02). The risk of bacteremia from any cause was higher in the heparin group than in the rt-PA group by a factor of 3 (hazard ratio, 3.30; 95% CI, 1.18 to 9.22; P = 0.02). The risk of adverse events, including bleeding, was similar in the two groups.” (B. R. Hemmelgarn, brenda.hemmelgarn@albertahealthservices.ca)
This new approach tackles “the Achilles’ heel of hemodialysis,” an editorialist explains (
pp. 372–4): “Given this new evidence, one can expect that dialysis providers will swiftly adopt the strategy of using rt-PA once a week. The once-weekly rt-PA strategy has the additional value of accessibility. Dialysis units already use rt-PA, although the use is based more on experience than on evidence, and can incorporate this proven treatment regimen in their standard-of-care protocols immediately. It is important to note, however, that rt-PA may invalidate certain laboratory measurements (e.g., parathyroid hormone and phosphate levels) when the blood used for those measurements is drawn through the central venous catheter, and so routine laboratory blood drawings should be scheduled accordingly.” (W. C. Winkelmayer)
Treatment of Hepatitis Delta: In about one-quarter of 31 patients with chronic infection of hepatitis B virus and hepatitis delta virus (HDV), 48 weeks of peginterferon alfa-2a, with or without adefovir, produced a sustained HDV RNA clearance (pp. 322–31). HDV, a defective RNA virus, requires coinfection with hepatitis B virus to replicate. Peginterferon alfa-2a 180 mcg weekly and/or adefovir 10 mg daily had these effects: “The primary end point—normalization of alanine aminotransferase levels and clearance of HDV RNA at week 48—was achieved in two patients in the group receiving peginterferon alfa-2a plus adefovir and two patients in the group receiving peginterferon alfa-2a plus placebo but in none of the patients in the group receiving adefovir alone. At week 48, the test for HDV RNA was negative in 23% of patients in the first group, 24% of patients in the second, and none of those in the third (P = 0.006 for the comparison of the first and third groups; P = 0.004 for the comparison of the second and third). The efficacy of peginterferon alfa-2a was sustained for 24 weeks after treatment, with 28% of the patients receiving peginterferon alfa-2a plus adefovir or peginterferon alfa-2a alone having negative results on HDV-RNA tests; none of the patients receiving adefovir alone had negative results. A decline in HBsAg levels of more than 1 log10 IU per milliliter from baseline to week 48 was observed in 10 patients in the first group, 2 in the second, and none in the third (P < 0.001 for the comparison of the first and third groups and P = 0.01 for the comparison of the first and second).” (M. P. Manns, manns.michael@mh-hannover.de)
Genomics & Cancer Care: Authors review the impact of genomics on cancer care (pp. 340–50): “Some of the early fruits of this research, along with the techniques needed to implement them, are already being incorporated into clinical oncology. Here, we review the effects that genomic approaches are having on tumor classification, prognostic markers, predictive indicators of drug response, the development of new drug therapies, strategies for monitoring disease, and the management of susceptibility to cancer.” (M. R. Stratton, mrs@sanger.ac.uk)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Jan. 28, 2011 * Vol. 18, No. 19
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Feb. issue of Diabetes Care (2011; 34).
Basal v. Insulin Lispro Mix: In patients with type 2 diabetes, twice-daily insulin lispro mix 75/25 (LM75/25) provided a “modestly longer durability of glycemic control,” compared with once-daily insulin glargine, according to DURABLE trial investigators (pp. 249–55). Patients were randomized to one of the two treatments for 6 months. Those with A1C levels of 7.0% or less were maintained on that treatment for up to 24 months, with these results: “Of 900 patients receiving LM75/25 and 918 patients receiving glargine who completed initiation, 473 and 419, respectively, had A1C ≤7.0% and continued into maintenance. Baseline characteristics except age were similar in this group. Median time of maintaining the A1C goal was 16.8 months for LM75/25 (95% CI 14.0–19.7) and 14.4 months for glargine (95% CI 13.4–16.8; P = 0.040). A1C goal was maintained in 202 LM75/25-treated patients (43%) and in 147 glargine-treated patients (35%; P = 0.006). No differences were observed in overall, nocturnal, or severe hypoglycemia. LM75/25 patients had higher total daily insulin dose (0.45 ± 0.21 vs. 0.37 ± 0.21 units/kg/day) and more weight gain (5.4 ± 5.8 vs. 3.7 ± 5.6 kg) from baseline. Patients taking LM75/25 and glargine with lower baseline A1C levels were more likely to maintain the A1C goal (P = 0.043 and P < 0.001, respectively).” (J. B. Buse)
Basal-Bolus Insulin Therapy During Surgery: In the RABBIT 2 Surgery study, once-daily insulin glargine with glulisine before meals improved glycemic control and reduced hospital complications, compared with sliding-scale insulin (SSI) four times daily (pp. 256–61). In 211 patients with type 2 diabetes, these results were noted: “The mean daily glucose concentration after the 1st day of basal–bolus insulin and SSI was 145 ± 32 mg/dL and 172 ± 47 mg/dL, respectively (P < 0.01). Glucose readings <140 mg/dL were recorded in 55% of patients in basal–bolus and 31% in the SSI group (P < 0.001). There were reductions with basal–bolus as compared with SSI in the composite outcome [24.3 and 8.6%; odds ratio 3.39 (95% CI 1.50–7.65); P = 0.003]. Glucose <70 mg/dL was reported in 23.1% of patients in the basal–bolus group and 4.7% in the SSI group (P < 0.001), but there were no significant differences in the frequency of BG <40 mg/dL between groups (P = 0.057).” (G. E. Umpierrez)
Low-Dose Aspirin Therapy & Renal Function: The benefits of low-dose aspirin in primary prevention of atherosclerotic events were evident among patients with moderately reduced renal function but not those with estimated glomerular filtration rates above 90 or below 60 mL/min/1.73 m2, report Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) authors (pp. 280–5). During a median of 4.37 years of aspirin 81 or 100 mg, 2,539 patients had these outcomes: “The incidence of primary end points was significantly lower in the aspirin group than in the nonaspirin group (aspirin, 30/661; nonaspirin, 55/712; hazard ratio 0.57 [95% CI 0.36–0.88]; P = 0.011). Low-dose aspirin therapy did not reduce primary end points in patients with eGFR ≥90 mL/min/1.73 m2 (aspirin, 9/248; nonaspirin, 11/270; 0.94 [0.38–2.3]) or those with eGFR <60 mL/min/1.73 m2 (aspirin, 29/342; nonaspirin, 19/290; 1.3 [0.76–2.4]). The Cox proportional hazard model demonstrated a significant interaction between mild renal dysfunction (eGFR 60–89 mL/min/1.73 m2) and aspirin (P = 0.02).” (Y. Saito)
Sexual Function & Bupropion Therapy: Reduced sexual function is common in patients with comorbid major depressive disorder (MDD) and type 2 diabetes, a study confirms, but bupropion treatment restore higher rates of sexual function (pp. 332–4): “At baseline, 71.1% of patients had insufficient [sexual function]. Mean Sexual Energy Scale (SES) scores improved during treatment (P < 0.0001), as did the percentage with sufficient [sexual function] (30.6 vs. 68.1%, P = 0.001). Patients with persistent hyperglycemia had higher rates of sexual dysfunction; however, SES improvement was evident in some with persistent depression or hyperglycemia (18.2% and 25.9%, respectively).” (G. S. Sayuk)
Perceptions About Illness & Medication Adherence: In 49 patients with type 1 diabetes and 108 patients with type 2 disease, perceptions about illness, medications, exercise, and diet were strongly associated with adherence to interventions (pp. 338–40; E. Broadbent).

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Jan. 31, 2011 * Vol. 18, No. 20
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Jan. 29 issue of Lancet (2011; 377).
Eltrombopag in Chronic Immune Thrombocytopenia: The oral thrombopoietin receptor agonist eltrombopag showed promise in management of chronic immune thrombocytopenia, with benefits especially notable in patients who did not respond to splenectomy or previous therapy, report RAISE trial investigators (pp. 393–402). In this Phase III trial, 197 adults with previously treated immune thrombocytopenia of more than 6 months’ duration and baseline platelet counts lower than 30,000/µL were randomly allocated to local standard of care plus eltrombopag 50 mg or placebo once daily for 6 months. Results showed: “106 (79%) patients in the eltrombopag group responded to treatment at least once during the study, compared with 17 (28%) patients in the placebo group. The odds of responding were greater in patients in the eltrombopag group compared with those in the placebo group throughout the 6-month treatment period (odds ratio 8.2, 99% CI 3.59—18.73; p < 0.0001). 37 (59%) patients receiving eltrombopag reduced concomitant treatment versus ten (32%) patients receiving placebo (p = 0.016). 24 (18%) patients receiving eltrombopag needed rescue treatment compared with 25 (40%) patients receiving placebo (p = 0.001). Three (2%) patients receiving eltrombopag had thromboembolic events compared with none in patients on placebo. Nine (7%) eltrombopag-treated patients and two (3%) in the placebo group had mild increases in alanine aminotransferase concentration, and five (4%) eltrombopag-treated patients (vs none allocated to placebo) had increases in total bilirubin. Four (7%) patients taking placebo had serious bleeding events, compared with one (<1%) patient treated with eltrombopag.” (G. Cheng, gcheng@cuhk.edu.hk)

>>>BMJ Highlights
Source:
Early-release articles from BMJ (2011; 342).
Vitamin D Supplements in Children: While children and adolescents with normal vitamin D levels are unlikely to benefit from supplements, bone density is likely increased in those with low levels, according to a systematic review and meta-analysis (c7254). The available evidence shows: “From 1,653 potential references, six studies, totalling 343 participants receiving placebo and 541 receiving vitamin D, contributed data to meta-analyses. Vitamin D supplementation had no statistically significant effects on total body bone mineral content or on bone mineral density of the hip or forearm. There was a trend to a small effect on lumbar spine bone mineral density (standardised mean difference 0.15, 95% confidence interval −0.01 to 0.31; P = 0.07). Effects were similar in studies of participants with high compared with low serum vitamin D levels, although there was a trend towards a larger effect with low vitamin D for total body bone mineral content (P = 0.09 for difference). In studies with low serum vitamin D, significant effects on total body bone mineral content and lumbar spine bone mineral density were roughly equivalent to a 2.6% and 1.7% percentage point greater change from baseline in the supplemented group.” (T. Winzenberg, tania.winzenberg@utas.edu.au)
Pay for Performance in Hypertension Therapy: In a setting where the quality of hypertension care was already stable or improving, addition of generous pay-for-performance incentives failed to further improve quality of care or outcomes of hypertension, researchers report (d108). Among 470,725 patients with hypertension diagnosed in 2004–07, an interrupted time-series analysis showed no changes in blood pressure monitoring, blood pressure control, or treatment intensity that could be attributed to pay for performance. In addition, no significant effects were found with respect to the incidence of several complications of hypertension, including stroke, myocardial infarction, renal or heart failure, or all-cause mortality. (S. B. Soumerai, stephen_soumerai@hms.harvard.edu)

>>>PNN JournalWatch
* Identification of ADAMTS7 as a Novel Locus for Coronary Atherosclerosis and Association of ABO with Myocardial Infarction in the Presence of Coronary Atherosclerosis: Two Genome-wide Association Studies, in Lancet, 2011; 377: 383–92. (M. P. Reilly, muredach@mail.med.upenn.edu)
* Closed-Loop Insulin Delivery During Pregnancy Complicated by Type 1 Diabetes, in
Diabetes Care, 2011; 34: 406–11. (H. R. Murphy, hm386@medschl.cam.ac.uk)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Feb. 1, 2011 * Vol. 18, No. 21
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Feb. 1 issue of the Annals of Internal Medicine (2011; 154).
2001 Adult Immunization Schedule: Updated vaccination recommendations for adults are reported by the Advisory Committee on Immunization Practices (ACIP) (pp. 168–73): “In October 2010, ACIP approved the Adult Immunization Schedule for 2011, which includes several changes. The notation for seasonal influenza vaccine in the [immunization schedule] and footnotes was changed to reflect the expanded recommendation for annual influenza vaccination for everyone 6 months of age or older, which was approved by ACIP in February 2010. In October 2010, ACIP issued a permissive recommendation for use of the tetanus, diphtheria, pertussis (Tdap) vaccine in adults aged 65 years or older; approved the recommendation that Tdap can be administered regardless of how much time has elapsed since the last tetanus and diphtheria (Td)–containing vaccine; and approved a recommendation for a 2-dose series of meningococcal vaccine in adults with certain high-risk medical conditions. The vaccines listed in the [immunization schedule] have been reordered to keep all universally recommended vaccines together (for example, influenza, Td/Tdap, varicella, human papillomavirus, and zoster).” (A. Shefer, ams7@cdc.gov)
An editorialist calls for better vaccination rates among health professionals (
pp. 204–6): “Universal influenza vaccination includes health care workers—all of us. In the past year, the American Medical Association, the Society for Healthcare Epidemiology of America with endorsement by the Infectious Diseases Society of America, the American Academy of Pediatrics, and the [American College of Physicians (ACP)] have strengthened their existing policies on influenza vaccination for health care workers. New ACP policy declares that ‘health care workers who cannot receive flu vaccines due to medical or religious contraindications should either be reassigned to non–patient care areas during influenza season or wear a mask at all times during influenza season in the context of patient care.’ Influenza vaccination of health care workers is undoubtedly a patient safety issue. We must each do our part to reach the goal of 100% flu vaccination. Get vaccinated today!” (S. A. Fryhofer)
Balancing Benefits, Harms & Costs of Care: Writing for a committee of the American College of Physicians, authors make these key points about ways of preserving “high-value, cost-conscious health care” (pp. 174–80). “First, assessing the benefits, harms, and costs of an intervention is essential to understand whether it provides good value. Second, assessing the cost of an intervention should include not only the cost of the intervention itself but also any downstream costs that occur because the intervention was performed. Third, the incremental cost-effectiveness ratio estimates the additional cost required to obtain additional health benefits and provides a key measure of the value of a health care intervention.” (A. Qaseem, aqaseem@acponline.org)
An editorialist retorts (
pp. 207–8): “[These authors] recognize that efforts to calculate value for money do not tell us how much to reduce health care spending. Because they presume that cost control is inevitable, they focus exclusively on how to make those cuts while maintaining high-quality care. Unfortunately, this ignores the opportunity costs that flow from applying the value-for-money principle in a country that has never mustered the political will to say ‘no’ to additional health care spending. Preserving ‘high-value, high-quality care’ while slowing the rate of cost increases will be a highwire act in the face of a steady stream of new and improved technologies, most of which may increase costs.” (M. K. Gusmano, gusmanom@thehastingscenter.org)

>>>PNN NewsWatch
* A federal judge’s declaration on Monday that the entire Affordable Care Act is unconstitutional presents the most serious challenge to date for President Obama’s signature legislative achievement. With four decisions split 2–2 about the law and dozens of other lawsuits on the way, the issue appears destined for a divided but generally conservative Supreme Court. Questions are how long will the cases take to get there (unless fast-tracked, the Court might not address the law for up to 2 years, observers are saying), what insurers and health care providers should or will do in the meantime, and how big of a mess will be created if the law is invalidated late in the process.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Feb. 2, 2011 * Vol. 18, No. 22
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Feb. 2 issue of JAMA (2011; 305).
DMARD Use in Rheumatoid Arthritis: In a study of Healthcare Effectiveness Data and Information Set (HEDIS) data in 2005–08, receipt of disease-modifying antirheumatic drugs (DMARDs) varied widely among patients with rheumatoid arthritis (RA), with lower usage in for-profit health plans, poorer patients, those living in ZIP Codes with low socioeconomic status, and those in Middle and South Atlantic regions of the U.S. (pp. 480–6). Men and blacks also received the drugs less frequently, the researchers add, noting these findings for 93,143 patients who were 65 years of age and had at least two diagnoses for RA within a measurement year: “The mean age of patients was 74 years; 75% were women and 82% were white. Overall performance on the HEDIS measure for RA was 59% in 2005, increasing to 67% in 2008 (P for trend <.001). The largest difference in performance was based on age: patients aged 85 years and older had a 30 percentage point lower rate of DMARD receipt (95% confidence interval [CI], −29 to −32 points; P < .001), compared with patients 65 to 69 years of age, even after adjusting for other factors. Lower percentage point rates were also found for patients who were men (−3 points; 95% CI, −5 to −2 points; P < .001), of black race (−4 points; 95% CI, −6 to −2 points; P < .001), with low personal income (−6 points; 95% CI, −8 to −5 points; P < .001), with the lowest zip code–based socioeconomic status (−4 points; 95% CI, −6 to 2 points; P < .001), or enrolled in for-profit health plans (−4 points; 95% CI, −7 to 0 points; P < .001); and in the Middle Atlantic region (−7 points; 95% CI, −13 to −2 points; P < .001) and South Atlantic regions (−11 points; 95% CI, −20 to −3 points; P < .001) as compared with the Pacific region. Performance varied widely by health plan, ranging from 16% to 87%.” (G. Schmajuk, schmajuk@gmail.com)
Mortality with Bevacizumab in Cancer: Increased treatment-related mortality is associated with bevacizumab use in cancer patients, a systematic review and meta-analysis shows (pp. 487–94). Prospective randomized controlled trials (RCTs) in which bevacizumab in combination with chemotherapy or biological therapy was compared with chemotherapy or biological therapy alone showed the following results for fatal adverse events (FAEs): “A total of 10,217 patients with a variety of advanced solid tumors from 16 RCTs were included in the analysis. The overall incidence of FAEs with bevacizumab was 2.5% (95% CI, 1.7%–3.9%). Compared with chemotherapy alone, the addition of bevacizumab was associated with an increased risk of FAEs, with an RR of 1.46 (95% CI, 1.09–1.94; P = .01; incidence, 2.5% vs 1.7%). This association varied significantly with chemotherapeutic agents (P = .045) but not with tumor types (P = .13) or bevacizumab doses (P = .16). Bevacizumab was associated with an increased risk of FAEs in patients receiving taxanes or platinum agents (RR, 3.49; 95% CI, 1.82–6.66; incidence, 3.3% vs 1.0%) but was not associated with increased risk of FAEs when used in conjunction with other agents (RR, 0.85; 95% CI, 0.25–2.88; incidence, 0.8% vs 0.9%). The most common causes of FAEs were hemorrhage (23.5%), neutropenia (12.2%), and gastrointestinal tract perforation (7.1%).” (S. Wu, shenhong.wu@stonybrook.edu)
An editorialist adds this perspective about use of bevacizumab in patients with solid tumors (
pp. 506–8): “Is bevacizumab a boon or a bust? The jury is still out. Although bevacizumab has benefit, it is currently not possible to determine in whom or for how long. Thus, oncologists are forced to dilute the potential effects of bevacizumab by exposing all treated patients, and society, to enormous costs and occasional life-threatening toxic effects. These unfortunate circumstances are sad for those who pay the bills—and sadder for patients with solid tumors.” (D. F. Hayes, hayesdf@umich.edu)

>>>PNN NewsWatch
* Patients who receive more than a 1-month supply of dabigatran need a way to mark “opened” or “use by” dates on the unit-of-use bottles, pharmacist.com reports. Pradaxa (Boehringer-Ingelheim) must be used within 30 days after the bottle is opened. Sarah A. Spinler, PharmD, of the University of the Sciences in Philadelphia, said that when patients open two bottles, they cannot use both within 30 days. If patients don’t know when each was opened, they may have to start over with a new bottle.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Feb. 3, 2011 * Vol. 18, No. 23
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Feb. 3 issue of the New England Journal of Medicine (2011; 364).
Efficacy of Quadrivalent HPV Vaccine in Males: In boys and men ages 16–26, vaccination against four subtypes of human papillomavirus reduced the occurrence of related external lesions, researchers report (pp. 401–11). The Merck-sponsored study of 4,065 participants in 18 countries provided three doses of a quadrivalent vaccine (active against HPV types 6, 11, 16, and 18) or placebo, with these results: “In the intention-to-treat population, 36 external genital lesions were seen in the vaccine group as compared with 89 in the placebo group, for an observed efficacy of 60.2% (95% confidence interval [CI], 40.8 to 73.8); the efficacy was 65.5% (95% CI, 45.8 to 78.6) for lesions related to HPV-6, 11, 16, or 18. In the per-protocol population, efficacy against lesions related to HPV-6, 11, 16, or 18 was 90.4% (95% CI, 69.2 to 98.1). Efficacy with respect to persistent infection with HPV-6, 11, 16, or 18 and detection of related DNA at any time was 47.8% (95% CI, 36.0 to 57.6) and 27.1% (95% CI, 16.6 to 36.3), respectively, in the intention-to-treat population and 85.6% (97.5% CI, 73.4 to 92.9) and 44.7% (95% CI, 31.5 to 55.6) in the per-protocol population. Injection-site pain was significantly more frequent among subjects receiving quadrivalent HPV vaccine than among those receiving placebo (57% vs. 51%, P < 0.001).” (A. R. Giuliano, anna.giuliano@moffitt.org)
While positive about these results, a Commentary author focuses on comparative effectiveness research and concludes that “improving the return on our health care investment is a vital imperative for the 21st century” (
pp. 393–5): “The report by Giuliano et al. undoubtedly gives us cause to celebrate the extraordinary potential for HPV vaccination to improve health in both women and men. And although enthusiasm for universal vaccination may initially be tempered by uncertainties about the vaccine’s safety, efficacy, and duration of protection (as well as its uptake, acceptability, and cost), many of these factors could very well change in the future. For example, the cost-effectiveness profile of routine vaccination of young men will improve if the evidence of efficacy continues to mount, the vaccine price declines, or coverage among girls and women remains low.” (J. J. Kim)
Fidaxomicin for C. difficile Infection: A macrocyclic antibiotic, fidaxomicin, produced significantly lower rates of recurrence of certain strains of Clostridium difficile, compared with vancomycin, in a Phase III trial of adults with acute symptoms and positive stool toxin tests (pp. 422–31). Fidaxomicin 200 mg twice daily or vancomycin 125 mg four times daily orally for 10 days showed these results: “A total of 629 patients were enrolled, of whom 548 (87.1%) could be evaluated for the per-protocol analysis. The rates of clinical cure with fidaxomicin were noninferior to those with vancomycin in both the modified intention-to-treat analysis (88.2% with fidaxomicin and 85.8% with vancomycin) and the per-protocol analysis (92.1% and 89.8%, respectively). Significantly fewer patients in the fidaxomicin group than in the vancomycin group had a recurrence of the infection, in both the modified intention-to-treat analysis (15.4% vs. 25.3%, P = 0.005) and the per-protocol analysis (13.3% vs. 24.0%, P = 0.004). The lower rate of recurrence was seen in patients with non–North American Pulsed Field type 1 strains. The adverse-event profile was similar for the two therapies.” (T. J. Louie, thomas.louie@albertahealthservices.ca)
An editorialist writes that fidaxomicin “appears to be an important advance” and adds (
pp. 473–5): “Future studies are needed to determine the relative value of various treatments in controlling symptoms of C. difficile infection and in preventing disease recurrences. Additional study is needed to determine the optimal duration of treatment for C. difficile infection. It is recommended that future trials of potentially curative treatments include the study of the metagenomic alterations of colonic microflora before and after treatment. It is likely that we will be better able to identify effective therapies for this emerging infectious disease if we have an enhanced understanding of the microbial community of the lower gut during episodes of C. difficile infection and at the time of recovery and more information regarding the selective pressure exerted by various antimicrobial agents directed against C. difficile infection.” (H. L. DuPont)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Feb. 4, 2011 * Vol. 18, No. 24
Providing news and information about medications and their proper use

>>>Pharmacotherapy Report
Source:
Feb. issue of Pharmacotherapy (2011; 31).
4Ts for HIT: In 80 consecutive patients suspected as having heparin-induced thrombocytopenia (HIT), the 4Ts clinical scoring system was useful and interrater reliability was fair, researchers report (pp. 138–45). The system relies on four clinical features of HIT—extent of thrombocytopenia, timing of platelet count fall, thrombosis or other sequelae, and identification of alternative causes of thrombocytopenia—to estimate patient risk. Using 4Ts results and values from polyspecific enzyme-linked immunosorbent assay (ELISA) tests in 2008–09, the investigators determined: “Sixty-seven (84%) of the 80 patients had low clinical probability of HIT based on the calculated 4Ts score. The ELISA result was negative for platelet factor 4–heparin antibodies in 74 patients (93%). Based on the results of the ELISA, the negative predictive value of the 4Ts score was 91%. Each 4Ts score was calculated by two independent investigators and adjudicated by a third investigator when necessary. The interrater reliability of the scoring system was fair (Cohen kappa coefficient 0.362, 95% confidence interval [CI] 0.222–0.502; weighted kappa coefficient 0.554 (95% CI 0.441–0.667). Determination of the timing of HIT was associated with the largest number of discrepancies (16) between evaluators, followed by other causes of thrombocytopenia (15), degree of decline in platelet count (14), and the presence of thrombosis or other sequelae (2).” (L. M. Sylvia, lsylvia1@tuftsmedicalcenter.org)
Outpatient Treatment of Pseudomonas aeruginosa Bronchial Colonization: The combination of inhaled colistin and tobramycin provided better clinical results than either agent alone in a group of adult patients without cystic fibrosis who had Pseudomonas aeruginosa bronchial colonization (pp. 146–57). In a prospective, observational study, investigators evaluated 97 courses of inhaled therapy used on an outpatient basis in 2004–08: “No significant differences between colistin and tobramycin were found in the mean number of hospital admissions, duration of hospitalizations, duration of antibiotic treatment, adverse events, mortality, or emergence of other opportunistic microorganisms. Emergence of resistance to colistin was lower than resistance to tobramycin (hazard ratio 0.09, 95% confidence interval [CI] 0.03–0.32). Patients treated with both inhaled antibiotics had fewer days of hospitalization and fewer days of antibiotic use than those treated with tobramycin alone (relative risk [RR] 0.33, 95% CI 0.10–1.12, and RR 0.27, 95% CI 0.08–0.93, respectively).” (D. Berlana, dberlana@hotmail.com)
Pharmacists in ICUs: Authors review the positive effects of pharmacists practicing on teams in critical-care areas (pp. 128–37): “There is substantial literature to support the value of the critical care pharmacist as a member of an interdisciplinary intensive care unit (ICU) team, particularly in terms of patient safety. Furthermore, a number of economic investigations have demonstrated cost savings or cost avoidance with pharmacist involvement. As the published evidence supporting pharmacist involvement in patient care activities in the ICU setting has increased, surveys have demonstrated an increase in the percentage of pharmacists performing clinical activities. In addition, substantial support of pharmacists has been provided by other clinicians, safety officers, and administrative personnel who have been involved with the initiation and expansion of critical care pharmacy services in their own institutions.” (B. L. Erstad, erstad@pharmacy.arizona.edu)

>>>PNN NewsWatch
* Updated warnings about cardiovascular risks of rosiglitazone (Avandia, GlaxoSmithKline) are now in product labeling of single- and multiple-drug products, FDA said yesterday. Rosiglitazone should be used only in patients already on the drug and in those whose blood glucose levels cannot be controlled with alternative medications and who do not wish to use pioglitazone, FDA added. These warnings were previously announced (see PNN, Sept. 24, 2010). The promised REMS for rosiglitazone has not yet been approved.
*
FDA has reminded clinicians that not all alcohol prep pads are sterile. Citing the Jan. 5 recall of Triad Group’s pads and swabs, FDA said health professionals and consumers should look for the word “sterile” on product labels when procedures require strict sterility.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Feb. 7, 2011 * Vol. 18, No. 25
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Early-release articles from BMJ (2011; 342).
Improving Patient Safety in Hospitals: Limited improvements in patient safety were observed following implementation of large-scale organizational interventions at four U.K. hospitals, researchers report (d195). During an initial 18-month phase of the Health Foundation’s Safer Patients Initiative (SPI1), interventions that focused on specific frontline care processes and organizational/cultural change had these effects: “Senior staff members were knowledgeable and enthusiastic about SPI1. There was a small (0.08 points on a 5 point scale) but significant (P < 0.01) effect in favour of the SPI1 hospitals in one of 11 dimensions of the staff questionnaire (organisational climate). Qualitative evidence showed only modest penetration of SPI1 at medical ward level. Although SPI1 was designed to engage staff from the bottom up, it did not usually feel like this to those working on the wards, and questions about legitimacy of some aspects of SPI1 were raised. Of the five components to identify patients at risk of deterioration—monitoring of vital signs (14 items); routine tests (three items); evidence based standards specific to certain diseases (three items); prescribing errors (multiple items from the British National Formulary); and medical history taking (11 items)—there was little net difference between control and SPI1 hospitals, except in relation to quality of monitoring of acute medical patients, which improved on average over time across all hospitals.… There were no improvements in the proportion of prescription errors and no effects that could be attributed to SPI1 in non-targeted generic areas (such as enhanced safety culture). On some measures, the lack of effect could be because compliance was already high at baseline (such as use of steroids in over 85% of cases where indicated), but even when there was more room for improvement (such as in quality of medical history taking), there was no significant additional net effect of SPI1. There were no changes over time or between control and SPI1 hospitals in errors or rates of adverse events in patients in medical wards.” (R. J. Lilford, r.j.lilford@bham.ac.uk)
Effectiveness of Pandemic Influenza Vaccine: In Canada, the monovalent pandemic influenza A/H1N1 vaccine was highly effective, a study shows, with results especially good following a single dose administered to children and young adults (c7297). Among 552 patients who presented within 7 days of symptom onset in four provinces, these results were recorded: “Pandemic H1N1 was detected by reverse transcription polymerase chain reaction in 209/552 (38%) participants; rates were highest in children and young adults (40%) and lowest in people aged 65 or over (9%). Among the 209 cases, 35 (17%) reported comorbidity compared with 80/343 (23%) controls. Two (1%) cases had received pandemic H1N1 vaccine at least two weeks before the onset of illness, compared with 58/343 (17%) controls, all single dose. Adjusted vaccine effectiveness overall was 93% (95% confidence interval 69% to 98%). High estimates of vaccine protection—generally at least 90%—were maintained across most sensitivity analyses.” (D. M. Skowronski, danuta.skowronski@bccdc.ca)

>>>PNN JournalWatch
* Comparison of Short-Course Multidrug Treatment with Standard Therapy for Visceral Leishmaniasis in India: An Open-Label, Non-Inferiority, Randomised Controlled Trial, in Lancet, 2011; 377: 477–86. (S. Sundar, drshyamsundar@hotmail.com)
* Propofol Addiction Initiated by Anesthetic Use [letter], in
American Journal of Psychiatry, 2011; 168: 211–2. (A. Koopman)
* Inhaled Nitric Oxide in Preterm Infants: A Systematic Review, in
Pediatrics, 2011; 127: e414–22. (P. K. Donohue)
* Recommended Childhood and Adolescent Immunization Schedules—United States, 2011, in
Pediatrics, 2011; 127: 387–8. (American Academy of Pediatrics Committee on Infectious Diseases)
* International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases, in
Clinical Infectious Diseases, 2011; 52: e103–20. (K. Gupta, kalpana.gupta@va.gov)
* Extemporaneous Compounding of Oral Liquid Dosage Formulations and Alternative Drug Delivery Methods for Anticancer Drugs, in
Pharmacotherapy, 2011; 31: 164–92. (M. S. H. Lam, sin.h.lam@kp.org)
* Contemporary Management of Transient Ischemic Attack: Role of the Pharmacist, in
Pharmacotherapy, 2011; 31: 193–213. (D. H. Rhoney, drhoney@wayne.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Feb. 8, 2011 * Vol. 18, No. 26
Providing news and information about medications and their proper use

>>>Pediatrics Highlights
Source:
Feb. issue of Pediatrics (2011; 127).
DHA Supplements in Preterm Infants: Compared with 44 historical control babies born prematurely who received soybean and olive oil supplements, 40 preterm neonates who received intravenous fish-oil emulsion supplements containing docosahexaenoic acid (DHA) had a significantly lower risk of requiring laser therapy for severe retinopathy, researchers report (pp. 223–8). The investigators found: “There was a significantly lower risk of laser therapy for infants who received an emulsion of soybean, olive oil, and fish oil (P = .023). No significant differences were found in acuity and latency of visual evoked potentials between infants in the 2 groups. There was no infant with cholestasis among those who received fish-oil emulsion, and there were 5 subjects with cholestasis in the historical group (P = .056).” (D. Pawlik)
Varicella-Related Hospitalizations: Reviewing U. S. data from the “1-dose varicella vaccination era,” authors found these patterns among 24,488 hospitalizations in 2000–06 (pp. 238–45): “The varicella-related hospitalization rate was 0.12 per 10,000 population during the 1-dose vaccination era versus 0.42 per 10,000 population in the prevaccination era (P < .01). During the 1-dose vaccination era, the estimated annual average number of varicella-related hospitalizations was significantly lower and decreased by 65% in all age groups compared with those in the prevaccination era (P < .001 in all age groups). The varicella-related hospitalization rate during the 1-dose vaccination era estimated from the Nationwide Inpatient Sample was 0.09 per 10,000 population.” (A. S. Lopez)

>>>Psychiatry Report
Source:
Feb. issue of the American Journal of Psychiatry (2011; 168).
Mortality with Second-Generation Antipsychotics: Nonsuicidal mortality rates were statistically identical for ziprasidone and olanzapine in a “large simple trial” of 18,154 patients, the Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC) (pp. 193–201). Data from the open-label, randomized, postmarketing trial showed: “The incidence of nonsuicide mortality within 1 year of initiating pharmacotherapy was 0.91 for ziprasidone (N = 9,077) and 0.90 for olanzapine (N = 9,077). The relative risk was 1.02 (95% CI = 0.76–1.39). This finding was confirmed in numerous secondary and sensitivity analyses.”
The authors conclude: “Despite the known risk of QTc prolongation with ziprasidone treatment, the findings of this study failed to show that ziprasidone is associated with an elevated risk of nonsuicidal mortality relative to olanzapine in real-world use; the study excludes a relative risk larger than 1.39 with a high probability. However, the study was neither powered nor designed to examine the risk of rare events like torsade de pointes.” (B. L. Strom)
An editorialist comments on the utility of large simple trials (LSTs) such as this one (
pp. 117–9): “LSTs can and should have an important role in assessing the effectiveness of newly approved drugs compared with standard treatments in psychiatry. Little is known about the long-term effects of new drugs when they come to market. The relatively small and brief trials conducted to achieve regulatory approval are carefully designed to show short-term efficacy and safety but are clearly not concerned with long-term adverse effects. Even major safety problems, including increased risk of sudden cardiac death, may be undetected when a new drug is first available. The widespread use of patented new drugs in preference to existing treatments, based only on results from short-term registration trials and with minimal long-term safety data, is expensive and potentially dangerous.” (T. S. Stroup, :tss2119@columbia.edu)

>>>PNN NewsWatch
* FDA has approved hydroxyprogesterone caproate injection(Makena) for reducing preterm deliveries before 37 weeks of pregnancy. The indication, made under FDA’s accelerated approval regulations, must be confirmed in additional studies. The drug is administered weekly into the hip beginning in weeks 16 to 21 of pregnancy. Makena was developed by Hologic, Inc., and is being sold to KV Pharmaceutical Company later this week.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Feb. 9, 2011 * Vol. 18, No. 27
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Early-release article and Feb. 9 issue of JAMA (2011; 305).
Optimal Antidiabetic Medications: When patients are switched from rosiglitazone, clinicians need to think beyond in-class transfers to the other available thiazolidinedione (TZD), authors of a Commentary argue (doi: 10.1001/jama.2011.193): “Switching prescription drugs within the same therapeutic class has become increasingly common with tiered drug plan formularies. Therefore, both patients and physicians may see the switch from rosiglitazone to pioglitazone as simple, straightforward, and appropriate, because patients are receiving a similar drug without the increased risk of myocardial infarction. However, when replacing rosiglitazone, physicians should keep in mind the balance of known risks and benefits of all other available options, not just the within-class alternative, pioglitazone. Neither TZD matches the safety, tolerability, and low cost of metformin. To help patients make the most clinically sound decisions, the ramifications of rosiglitazone’s safety concerns must be reframed from simply substituting one agent in a treatment class for another to a critical evaluation of the appropriate use of TZDs in the diabetes regimen. It is time to think outside this class.” (K. J. Lipska, kasia.lipska@yale.edu)
Vaccine Antibody Responses of Infants Born to HIV-Infected Mothers: Exposed but uninfected infants of mothers with HIV infections have lower antibody responses to routine vaccinations, but they soon recover their responses, a study shows (pp. 576–84). In a community-based cohort study in South Africa, 109 mothers and their infants provided serum samples at birth. Follow-up samples of the infants were collected at 16 weeks. These patterns of maternal- and infant-specific antibody levels to Haemophilus influenzae type b (Hib), pneumococcus, Bordetella pertussis antigens, tetanus toxoid, and hepatitis B surface antigen were found: “At birth, HIV-exposed uninfected infants (n = 46) had lower levels of specific antibodies than unexposed infants (n = 54) did to Hib (0.37 [interquartile range {IQR}, 0.22–0.67] mg/L vs 1.02 [IQR, 0.34-3.79] mg/L; P < .001), pertussis (16.07 [IQR, 8.87–30.43] Food and Drug Administration [FDA] U/mL vs 36.11 [IQR, 20.41–76.28] FDA U/mL; P < .001), pneumococcus (17.24 [IQR, 11.33–40.25] mg/L vs 31.97 [IQR, 18.58–61.80] mg/L; P = .02), and tetanus (0.08 [IQR, 0.03–0.39] IU/mL vs 0.24 [IQR, 0.08–0.92] IU/mL; P = .006). Compared with HIV-uninfected women (n = 58), HIV-infected women (n = 46) had lower specific antibody levels to Hib (0.67 [IQR, 0.16–1.54] mg/L vs 1.34 [IQR, 0.15–4.82] mg/L; P = .009) and pneumococcus (33.47 [IQR, 4.03–69.43] mg/L vs 50.84 [IQR, 7.40–118.00] mg/L; P = .03); however, no differences were observed for antipertussis or antitetanus antibodies. HIV-exposed uninfected infants (n = 38) compared with HIV-unexposed infants (n = 55) had robust antibody responses following vaccination, with higher antibody responses to pertussis (270.1 [IQR, 84.4–355.0] FDA U/mL vs 91.7 [IQR, 27.9–168.4] FDA U/mL; P = .006) and pneumococcus (47.32 [IQR, 32.56–77.80] mg/L vs 14.77 [IQR, 11.06–41.08] mg/L; P = .001).” (C. E. Jones, christine.jones@imperial.ac.uk)
Surgical Management of Metastatic Breast Cancer: Commenting on a study suggesting that complete axillary lymph node dissection may not be necessary in women with breast cancer whose nodes are positive (pp. 569–75; A. E. Giuliano, giulianoa@jwci.org). editorialists write (pp. 606–7): “Giuliano and colleagues have made an important contribution to the surgical management of [sentinel lymph node (SLN)] metastasis in breast cancer. Following the lead of Fisher et al and other clinical investigators, these randomized clinical trials have shown that less surgery combined with more radiation and chemotherapy have improved survival for women with breast cancer. Taken together, findings from these investigators provide strong evidence that patients undergoing partial mastectomy, whole-breast irradiation, and systemic therapy for early breast cancer with microscopic SLN metastasis can be treated effectively and safely without [axillary lymph node dissection].” (G. W. Carlson, grant_carlson@emory.org)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Feb. 10, 2011 * Vol. 18, No. 28
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Feb. 10 issue of the New England Journal of Medicine (2011; 364).
Treatment of Pancreatic Neuroendocrine Tumors: Two research studies and an editorial explore innovative treatments for advanced pancreatic neuroendocrine tumors.
In 171 patients with advanced pancreatic neuroendocrine tumors, sunitinib improved survival and response rates, researchers report (
pp. 501–13). In the Phase III trial, patients within 12 months of diagnosis with advanced, well-differentiated pancreatic neuroendocrine tumors were randomly assigned to sunitinib 37.5 mg/day or placebo. Results showed: “The study was discontinued early, after the independent data and safety monitoring committee observed more serious adverse events and deaths in the placebo group as well as a difference in progression-free survival favoring sunitinib. Median progression-free survival was 11.4 months in the sunitinib group as compared with 5.5 months in the placebo group (hazard ratio for progression or death, 0.42; 95% confidence interval [CI], 0.26 to 0.66; P < 0.001). A Cox proportional-hazards analysis of progression-free survival according to baseline characteristics favored sunitinib in all subgroups studied. The objective response rate was 9.3% in the sunitinib group versus 0% in the placebo group. At the data cutoff point, 9 deaths were reported in the sunitinib group (10%) versus 21 deaths in the placebo group (25%) (hazard ratio for death, 0.41; 95% CI, 0.19 to 0.89; P = 0.02). The most frequent adverse events in the sunitinib group were diarrhea, nausea, vomiting, asthenia, and fatigue.” (E. Raymond, eric.raymond@bjn.aphp.fr)
Everolimus, an oral inhibitor of mammalian target of rapamycin (mTOR), improved progression-free survival with minimal serious adverse events in 410 patients with advanced, low-grade or intermediate-grade pancreatic neuroendocrine tumors (
pp. 514–23). The patients, whose tumors had all shown radiologic progression within the previous 12 months, received placebo or everolimus 10 mg/day, with these results: “The median progression-free survival was 11.0 months with everolimus as compared with 4.6 months with placebo (hazard ratio for disease progression or death from any cause with everolimus, 0.35; 95% confidence interval [CI], 0.27 to 0.45; P < 0.001), representing a 65% reduction in the estimated risk of progression or death. Estimates of the proportion of patients who were alive and progression-free at 18 months were 34% (95% CI, 26 to 43) with everolimus as compared with 9% (95% CI, 4 to 16) with placebo. Drug-related adverse events were mostly grade 1 or 2 and included stomatitis (in 64% of patients in the everolimus group vs. 17% in the placebo group), rash (49% vs. 10%), diarrhea (34% vs. 10%), fatigue (31% vs. 14%), and infections (23% vs. 6%), which were primarily upper respiratory. Grade 3 or 4 events that were more frequent with everolimus than with placebo included anemia (6% vs. 0%) and hyperglycemia (5% vs. 2%). The median exposure to everolimus was longer than exposure to placebo by a factor of 2.3 (38 weeks vs. 16 weeks).” (J. C. Yao, jyao@mdanderson.org)
Editorialists are cautious but hopeful about these findings (
pp. 564–5): “These studies provide optimism regarding the treatment of malignant pancreatic neuroendocrine tumors, because both drugs are effective at improving disease-free survival, even in patients in whom other treatments have failed, and thus offer effective therapies where there were none before; however, the studies also raise some important unanswered questions that make the optimism guarded.… If patients no longer have a response to one drug, can they then be effectively treated with the other drug or with a combination of the two drugs? Can these drugs be used as neoadjuvant or adjuvant therapy (with surgery) or in combination with peptide-receptor radionuclide therapy or somatostatin analogue therapy? Finally, it is unclear how the side-effect profiles will affect long-term adherence to treatment. The drug-related side effects that develop in a patient with a malignant pancreatic endocrine tumor are particularly important to consider, given that treatment will be long term and that many patients have an excellent quality of life with no treatment until late in the disease course, even with advanced disease that is progressive.” (R. T. Jensen)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Feb. 11, 2011 * Vol. 18, No. 29
Providing news and information about medications and their proper use

>>>Circulation Highlights
Source:
Feb. 8 issue of Circulation (2011; 123).
Clopidogrel & PPIs: Risk of cardiovascular events or mortality was not increased with clopidogrel use with proton-pump inhibitors, researchers report (pp. 474–82). The findings held regardless of patients’ CYP2C19 genotypes, but “harm could not be formally excluded in patients with 2 loss-of-function alleles.” In the French Registry of Acute ST-Elevation and Non–ST-Elevation Myocardial Infarction (FAST-MI), patients with definite myocardial infarctions had these outcomes according to clopidogrel or PPI use within 48 hours of hospital admission: “PPI use was not associated with an increased risk for any of the main in-hospital events (in-hospital survival, reinfarction, stroke, bleeding, and transfusion). Likewise, PPI treatment was not an independent predictor of 1-year survival (hazard ratio, 0.97; 95% confidence interval [CI], 0.87 to 1.08; P=0.57) or 1-year MI, stroke, or death (hazard ratio, 0.98; 95% CI, 0.90 to 1.08; P=0.72). No differences were seen when the type of PPI or CYP2C19 genotype was taken into account. In the propensity-matched cohorts, the odds ratios for major in-hospital events in PPI versus no PPI were 0.29 (95% CI, 0.06 to 1.44) and 1.70 (95% CI, 0.10 to 30.3) for patients with 1 and 2 variant alleles, respectively. Similarly, the hazard ratio for 1-year events in hospital survivors was 0.68 (95% CI, 0.26 to 1.79) and 0.55 (95% CI, 0.06 to 5.30), respectively.” (T. Simon, tabassome.simon@sat.aphp.fr)

>>>Cardiology Highlights
Source:
Feb. 15 issue of the Journal of the American College of Cardiology (2011; 57).
Cost-Effectiveness of CRP Testing & Rosuvastatin Therapy with Normal Cholesterol Levels: In a study of the cost implications of implementing JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) findings in clinical practice, researchers conclude that, in patients with Framingham scores of 10% or more and normal LDL cholesterol levels, testing for high-sensitivity C-reactive protein (hs-CRP) and rosuvastatin therapy for those with elevated levels is cost-effective (pp. 784–91). Using a model that include men 50 and older and women 60 and older with LDL cholesterol levels less than 130 mg/dL, the investigators found these costs of hs-CRP testing followed by rosuvastatin therapy in those with levels of 2 mg/L or more, compared with usual care: “Rosuvastatin had an incremental cost-effectiveness of $25,198 per quality-adjusted life year (QALY) gained compared to usual care. If the effectiveness of rosuvastatin were 50% of that observed in JUPITER, the incremental cost-effectiveness ratio would increase to $50,871 per QALY. Implementing this strategy only in patients with a Framingham risk score ≥10% yielded an incremental cost-effectiveness of $14,205 per QALY. Among such intermediate-risk patients, a JUPITER-based strategy becomes cost-saving at a rosuvastatin price of <$0.86 per day.” (N. K. Choudhry, nchoudhry@partners.org)
An editorialist notes that, cost-effectiveness aside, costs are costs (
pp. 792–3): “It is essential to remember that a cost-effective therapy actually costs more money, not less. Prevention rarely saves money, despite the wishes of some that it did. It has been estimated that between 6 million and 12 million patients might begin statin treatment based on JUPITER results. Choudhry et al. estimate that such treatment would increase lifetime health care costs by $7,900 per person, even after factoring in generic rosuvastatin prices and later cost saving from preventing heart disease. Putting these figures together implies it would cost between $50 billion and $95 billion to extend rosuvastatin therapy to JUPITER-eligible patients in the U.S. Are we convinced this is the best use of these health care dollars?” (M. A. Hlatky, hlatky@stanford.edu)
Fatty Acids in Cardiomyopathy: A small trial justifies further study of n-3 polyunsaturated fatty acids (PUFAs) effects on left ventricular (LV) systolic function in patients with chronic heart failure due to nonischemic dilated cardiomyopathy (pp. 870–9). After 12 months of n-3 PUFA 2 g daily or placebo, significant improvements were found for LV ejection fraction, peak oxygen uptake, exercise duration, and mean New York Heart Association functional class. In addition, hospitalization rates were lower with n-3 PUFA, 6% versus 30% with placebo. (M. Gheorghiade, m-gheorghiade@northwestern.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Feb. 14, 2011 * Vol. 18, No. 30
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Feb. 12 issue of Lancet (2011; 377).
Global Trends in Obesity, Blood Pressure, & Cholesterol: Three articles report trends since 1980 for key aspects of health.
Globally, body mass index increased between 1980 and 2008 but with substantial variations among nations, a study shows (
pp. 557–67). Published and unpublished health examination surveys and epidemiological studies provided 960 country–years of data for 9.1 million participants, showing: “Mean BMI worldwide increased by 0.4 kg/m2 per decade (95% uncertainty interval 0.2–0.6, posterior probability of being a true increase >0.999) for men and 0.5 kg/m2 per decade (0.3–0.7, posterior probability > 0.999) for women. National BMI change for women ranged from non-significant decreases in 19 countries to increases of more than 2.0 kg/m2 per decade (posterior probabilities >0.99) in nine countries in Oceania.”
Systolic blood pressures decreased slightly over this time period, leaving low- and middle-income countries with the greatest proportions of people with high levels (
pp. 568–77): “In 2008, age-standardised mean SBP worldwide was 128.1 mm Hg (95% uncertainty interval 126.7–129.4) in men and 124.4 mm Hg (123.0–125.9) in women. Globally, between 1980 and 2008, SBP decreased by 0.8 mm Hg per decade (–0.4 to 2.2, posterior probability of being a true decline = 0.90) in men and 1.0 mm Hg per decade (–0.3 to 2.3, posterior probability = 0.93) in women. Female SBP decreased by 3.5 mm Hg or more per decade in western Europe and Australasia (posterior probabilities ≥ 0.999). Male SBP fell most in high-income North America, by 2.8 mm Hg per decade (1.3–4.5, posterior probability > 0.999), followed by Australasia and western Europe where it decreased by more than 2.0 mm Hg per decade (posterior probabilities > 0.98). SBP rose in Oceania, east Africa, and south and southeast Asia for both sexes, and in west Africa for women, with the increases [of] 0.8–1.6 mm Hg per decade in men (posterior probabilities 0.72–0.91) and 1.0–2.7 mm Hg per decade for women (posterior probabilities 0.75–0.98). Female SBP was highest in some east and west African countries, with means of 135 mm Hg or greater. Male SBP was highest in Baltic and east and west African countries, where mean SBP reached 138 mm Hg or more. Men and women in western Europe had the highest SBP in high-income regions.”
Serum cholesterol levels are rising in Asian countries, the data show, and better nutrition and increased use of medications could further improve values in countries where decreases have occurred (
pp. 578–86): “In 2008, age-standardised mean total cholesterol worldwide was 4.64 mmol/L (95% uncertainty interval 4.51–4.76) for men and 4.76 mmol/L (4.62–4.91) for women. Globally, mean total cholesterol changed little between 1980 and 2008, falling by less than 0.1 mmol/L per decade in men and women. Total cholesterol fell in the high-income region consisting of Australasia, North America, and western Europe, and in central and eastern Europe; the regional declines were about 0.2 mmol/L per decade for both sexes, with posterior probabilities of these being true declines 0.99 or greater. Mean total cholesterol increased in east and southeast Asia and Pacific by 0.08 mmol/L per decade (–0.06 to 0.22, posterior probability = 0.86) in men and 0.09 mmol/L per decade (–0.07 to 0.26, posterior probability = 0.86) in women. Despite converging trends, serum total cholesterol in 2008 was highest in the high-income region consisting of Australasia, North America, and western Europe; the regional mean was 5.24 mmol/L (5.08–5.39) for men and 5.23 mmol/L (5.03–5.43) for women. It was lowest in sub-Saharan Africa at 4.08 mmol/L (3.82–4.34) for men and 4.27 mmol/L (3.99–4.56) for women.” (M. Ezzati, majid.ezzati@imperial.ac.uk)

>>>PNN JournalWatch
* The Emerging Role of Interleukin-1-beta in Autoinflammatory Diseases, in Arthritis & Rheumatism, 2011; 63: 314–24. (H. J. Lachmann, h.lachmann@medsch.ucl.ac.uk)
* Should Bisphosphonates Be Used for Long-term Treatment of Glucocorticoid-Induced Osteoporosis?, in
Arthritis & Rheumatism, 2011; 63: 325–8. (S. L. Teitelbaum, teitelbs@wustl.edu)
* Current and Novel Therapeutics in the Treatment of Systemic Lupus Erythematosus, in
Journal of Allergy and Clinical Immunology, 2011; 127: 303–12. (B. Diamond, bdiamond@nshs.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Feb. 15, 2011 * Vol. 18, No. 31
Providing news and information about medications and their proper use

>>>Internal Medicine Report I
Source:
Early-release article from and Feb. 15 issue of the Annals of Internal Medicine (2011; 154).
Optimizing HIV Therapy: A once-daily ritonavir-boosted protease inhibitor regimen performed similarly to once-daily efavirenz-based treatments in antiretroviral-naive patients with HIV-1 infections, researchers report (early release). Adverse effects were fewer when ritonavir was combined with abacavir–lamivudine than with tenofovir disoproxil fumarate (DF)–emtricitabine, the investigators noted, adding these details about patients at 59 AIDS Clinical Trials Group sites in the U.S. and Puerto Rico: “Eligible patients randomly assigned to atazanavir plus ritonavir versus efavirenz with abacavir–lamivudine were 463 and 465, with 322 (70%) and 324 (70%) completing follow-up, respectively. Total participants who received tenofovir DF–emtricitabine were 465 and 464, with 342 (74%) and 343 (74%) completing follow-up, respectively. Primary efficacy [time to virologic failure, safety, and tolerability events.] was similar between the groups who received atazanavir plus ritonavir and efavirenz with abacavir–lamivudine or tenofovir DF–emtricitabine. Hazard ratios for time to virologic failure were 1.13 (95% CI, 0.82 to 1.56) and 1.01 (CI, 0.70 to 1.46), respectively; although CIs did not meet prespecified criteria for equivalence. There was a longer time to safety (P = 0.048) and tolerability (P < 0.001) events in persons given atazanavir plus ritonavir than efavirenz with abacavir–lamivudine but not with tenofovir DF–emtricitabine.” (E. S. Daar, EDaar@LABioMed.org)
Intensive Insulin Therapy in Hospitalized Patients: In an evidence-based Clinical Practice Guideline, the American College of Physicians (ACP) makes three recommendations (pp. 260–7; A. Qaseem):
* ACP recommends not using intensive insulin therapy to strictly control blood glucose in non–surgical intensive care unit (SICU)/medical intensive care unit (MICU) patients with or without diabetes mellitus (Grade: strong recommendation, moderate-quality evidence).
* ACP recommends not using intensive insulin therapy to normalize blood glucose in SICU/MICU patients with or without diabetes mellitus (Grade: strong recommendation, high-quality evidence).
* ACP recommends a target blood glucose level of 7.8 to 11.1 mmol/L (140 to 200 mg/dL) if insulin therapy is used in SICU/MICU patients (Grade: weak recommendation, moderate-quality evidence).

>>>Internal Medicine Report II
Source:
Early-release article from and Feb. 14 issue of the Archives of Internal Medicine (2011; 171).
PPI–Alendronate Interaction: Patients lose the bone-protecting effects of alendronate when on concurrent proton-pump inhibitors, according to results of a register-based, open cohort study (doi: 10.1001/archinternmed.2011.20). While not designed to infer causality, the research provides these correlations in 38,088 new users of alendronate during a mean of 3.5 years of follow-up: “For hip fractures, there was statistically significant interaction with alendronate for PPI use (P < .05). The treatment response associated with complete refill compliance to alendronate was a 39% risk reduction (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.52–0.71; P < .001) in patients who were not PPI users, while the risk reduction in concurrent PPI users was not significant (19%; HR, 0.81; 95% CI, 0.64–1.01; P = .06). The attenuation of the risk reduction was dose and age dependent. In contrast, there was no significant impact of concurrent use of histamine H2 receptor blockers.” (B. Abrahamsen, b.abrahamsen@physician.dk)
Adding PPIs to Aspirin: Aspirin proved less costly and more effective than no treatment among older men with at least a 10% risk of coronary heart disease, a study shows, but adding PPIs to prevent adverse effects was cost-effective only for those at high risk (pp. 218–25): “In 45-year-old men with a 10-year CHD risk of 10% and 0.8 per 1,000 annual GI bleeding risk, aspirin ($17 571 and 18.67 quality-adjusted life–years [QALYs]) was more effective and less costly than no treatment ($18,483 and 18.44 QALYs). Compared with aspirin alone, aspirin plus PPI ($21,037 and 18.68 QALYs) had an incremental cost per QALY of $447,077. Results were similar in 55- and 65-year-old men. The incremental cost per QALY of adding a PPI was less than $50,000 per QALY at annual GI bleeding probabilities greater than 4 to 6 per 1,000.” (S. R. Earnshaw, searnshaw@rti.org)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Feb. 16, 2011 * Vol. 18, No. 32
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Feb. 16 issue of JAMA (2011; 305).
Hospital Readmission Rates & Health Disparities: Among elderly Medicare beneficiaries hospitalized in 2006–08 for acute myocardial infarction (MI), congestive heart failure (CHF), or pneumonia, blacks were more likely to be readmitted within 30 days, compared with whites, researchers report (pp. 675–81). The difference was found both in hospitals primarily serving minorities and other facilities, as follows: “Overall, black patients had higher readmission rates than white patients (24.8% vs 22.6%, odds ratio [OR], 1.13; 95% confidence interval [CI], 1.11–1.14; P < .001); patients from minority–serving hospitals had higher readmission rates than those from non–minority-serving hospitals (25.5% vs 22.0%, OR, 1.23; 95% CI, 1.20–1.27; P < .001). Among patients with acute MI and using white patients from non−minority-serving hospitals as the reference group (readmission rate 20.9%), black patients from minority-serving hospitals had the highest readmission rate (26.4%; OR, 1.35; 95% CI, 1.28–1.42), while white patients from minority-serving hospitals had a 24.6% readmission rate (OR, 1.23; 95% CI, 1.18–1.29) and black patients from non−minority-serving hospitals had a 23.3% readmission rate (OR, 1.20; 95% CI, 1.16–1.23; P < .001 for each); patterns were similar for CHF and pneumonia. The results were unchanged after adjusting for hospital characteristics including markers of caring for poor patients.” (K. E. Joynt, kjoynt@partners.org)
With provisions of the Affordable Care Act on the horizon, editorialists note the need for hospitals to address both internal and external causes of unnecessary readmissions (
pp. 715–6): “Until the factors that increase a patient’s risk for readmission and until questions about how the health care system fails beyond the hospital’s door are better understood, hospital readmissions will continue to drain the health care system. Sources of evidence on how to prevent readmissions must range from comparative studies of health care delivery systems to randomized clinical trials of specific interventions. The consequences of policies that inadvertently reward the rich and penalize the poor must be carefully considered, especially given the thin evidence base on which readmission reduction strategies rest. As new systems of care are developed, the disparities gap must be closed so that improvements in quality are shared by everyone.” (A. F. Hernandez, adrian.hernandez@duke.edu)
Readmissions in Pediatric Hospitals: Just 2.9% of patients with frequent readmissions account for 18.8% of admissions and 23.2% of inpatient charges in pediatric hospitals, a study shows (pp. 682–90). In a retrospective cohort analysis of nearly 318,000 patients admitted to 37 U.S. children’s hospitals in 2003, with follow-up through 2008, investigators found: “In the sample, 69,294 patients (21.8%) experienced at least 1 readmission within 365 days of a prior admission. Within a 365-day interval, 9,237 patients (2.9%) experienced 4 or more readmissions; time between admissions was a median 37 days (interquartile range [IQR], 21–63). These patients accounted for 18.8% (109,155 admissions) of all admissions and 23.2% ($3.4 billion) of total inpatient charges for the study cohort during the entire follow-up period.” (J. G. Berry, jay.berry@childrens.harvard.edu)
“Me-Too” Drugs: Commentary authors call for changes in FDA standards for me-too agents once innovator agents in a class are available generically (pp. 711–2): “After this, manufacturers seeking FDA approval should explicitly demonstrate the superiority of the new product, not just its noninferiority, compared with other products that are already available. Superiority could be based on clear improvements in efficacy or safety. Or indications could be sought for populations other than those for which existing drugs in the class are approved, such as elderly persons or children (where appropriate). Another option would be to seek a new indication altogether.” (N. K. Choudhry, nchoudhry@partners.org)

>>>PNN NewsWatch
* Reversing a previous conclusion, the Cochrane Library says that zinc supplements reduce the severity and duration of symptoms of the common cold. In 15 trials of 1,360 people, significantly more of those taking zinc syrup, lozenges, or tablets were free of symptoms at 7 days.
*
Correction: In last Friday’s article on fatty acids, significant improvements, not decreases, were found in several variables.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Feb. 17, 2011 * Vol. 18, No. 33
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Feb. 17 issue of the New England Journal of Medicine (2011; 364).
Intravitreal Bevacizumab for Retinopathy of Prematurity: In a small trial, intravitreal bevacizumab reduced recurrence of stage 3+ retinopathy of prematurity, compared with conventional laser therapy (pp. 603–15). Depending on the degree of prematurity, retinopathy affects an inner circle, zone I, surrounding the optic nerve, or an outer circular zone II. In the trial, powered only to assess efficacy, premature infants with zone I or II posterior stage 3+ retinopathy of prematurity received bilaterally either intravitreal bevacizumab 0.625 mg or conventional laser therapy, with these results: “We enrolled 150 infants (total sample of 300 eyes); 143 infants survived to 54 weeks’ postmenstrual age, and the 7 infants who died were not included in the primary-outcome analyses. Retinopathy of prematurity recurred in 4 infants in the bevacizumab group (6 of 140 eyes [4%]) and 19 infants in the laser-therapy group (32 of 146 eyes [22%], P = 0.002). A significant treatment effect was found for zone I retinopathy of prematurity (P = 0.003) but not for zone II disease (P = 0.27).” (H.A. Mintz-Hittner, helen.a.mintz-hittner@uth.tmc.edu)
Despite the lack of safety data for bevacizumab, an editorialist endorses use of the agent for zone I disease based on the weight of evidence showing it is at least as safe as laser therapy (
pp. 677–8): “In light of previous work and its confirmation in a robust clinical trial, the use of intravitreal bevacizumab as monotherapy is superior to laser therapy in treating zone I retinopathy of prematurity and is possibly superior in treating posterior zone II disease. I speculate that intravitreal bevacizumab therapy will prove to be at least equal to laser therapy in clinical effectiveness for most forms of retinopathy of prematurity. As our experience with bevacizumab grows, its indications and relative contraindications will be refined. In the meantime, intravitreal bevacizumab should become the treatment of choice for zone I retinopathy of prematurity.” (J. D. Reynolds)
Safety of Pandemic Influenza Vaccine in China: Administration of 10 formulations of 2009 pandemic influenza A/H1N1 vaccine was not associated with serious adverse events, including Guillain-Barré syndrome, in China, researchers report (pp. 638–47). Passive surveillance by the Chinese CDC and associated local organizations showed the following: “A total of 89.6 million doses of vaccine were administered from September 21, 2009, through March 21, 2010, and 8,067 vaccinees reported having an adverse event, for a rate of 90.0 per 1 million doses. The age-specific rates of adverse events ranged from 31.4 per 1 million doses among persons 60 years of age or older to 130.6 per 1 million doses among persons 9 years of age or younger, and the manufacturer-specific rates ranged from 4.6 to 185.4 per 1 million doses. A total of 6,552 of the 8,067 adverse events (81.2%; rate, 73.1 per 1 million doses) were verified as vaccine reactions; 1,083 of the 8,067 (13.4%; rate, 12.1 per 1 million doses) were rare and more serious (vs. common, minor events), most of which (1,050) were allergic reactions. Eleven cases of the Guillain–Barré syndrome were reported, for a rate of 0.1 per 1 million doses, which is lower than the background rate in China.” (Y. Wang, wangyu@chinacdc.cn)
Closing the Part D Doughnut Hole: The health care reform law will make Medicare Part D even more complex while it incrementally closes the coverage gap (pp. 598–601): “The new benefit does represent a route to a coverage system that could well enhance the health of seniors. Over the next 10 years, physicians, nurses, pharmacists, and payers must play a role in helping patients to understand their options and in promoting appropriate medication use.” (W. H. Shrank)

>>>PNN NewsWatch
* U.S. Marshals, acting yesterday at FDA’s request, seized all lots of Auralgan Otic Solution stored at Integrated Commercialization Solutions. The product, manufactured by Deston Therapeutics, is an unapproved new drug, FDA said. The agency said it had warned Deston three times during 2010 and once early this month that it was distributing unapproved new drugs and misbranded drugs.
* Two recent
FDA recalls affect hospitals: Medtronic SynchroMed II and SynchroMed EL implantable infusion pumps and refill kits and potentially nonsterile Triad lubricating jelly products.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Feb. 18, 2011 * Vol. 18, No. 34
Providing news and information about medications and their proper use

>>>Oncology Highlights
Source:
Feb. 20 issue of the Journal of Clinical Oncology (2011; 29).
CHF with Bevacizumab: Use of bevacizumab in patients with breast cancer is associated with a significant increase in risk of congestive heart failure, a meta-analysis shows (pp. 632–8). Authors used data on 3,784 patients described in the published literature or at major oncology conferences to determine: “Overall incidence results for high-grade CHF in bevacizumab- and placebo-treated patients were 1.6% (95% CI, 1.0% to 2.6%) and 0.4% (95% CI, 0.2% to 1.0%), respectively. The RR of CHF in bevacizumab-treated patients was 4.74 (95% CI, 1.66 to 11.18; P = .001) compared with placebo-treated ones. In subgroup analyses, there were no significant differences in CHF incidence or risk between patients treated with low-dose (2.5 mg/kg) versus high-dose (5 mg/kg) bevacizumab or among patients treated with different chemotherapy regimens. No evidence of publication bias was observed.” (F. A. B. Schutz, FabioA_Schutz@dfci.harvard.edu)
Individualized Care for Patients with Advanced Cancer: The “complex physical, psychological, social, and spiritual consequences of… advanced incurable cancer” require individualized care, according to the American Society of Clinical Oncology (pp. 755–60): “This statement advocates an individualized approach to discussing and providing disease-directed and supportive care options for patients with advanced cancer throughout the continuum of care. Building on ASCO’s prior statements on end-of-life care (1998) and palliative care (2009), this article reviews the evidence for improved patient care in advanced cancer when patients’ individual goals and preferences for care are discussed. It outlines the goals for individualized care, barriers that currently limit realization of this vision, and possible strategies to overcome these barriers that can improve care consistent with the goals of our patients and evidence-based medical practice.” (J. Peppercorn, jeffrey.peppercorn@duke.edu)

>>>Nephrology Report
Source:
Feb. issue of the American Journal of Kidney Diseases (2011; 57).
Heart Failure in Dialysis Patients: In patients with chronic kidney disease who are treated with dialysis, cardiovascular events occur at 2 to 10 times the rate in matched patients with normal kidney function, and many of the affected patients have heart failure, authors of a review write (pp. 308–19): “Unlike in the general population, very few advances have been made in managing this severe complication in dialysis patients. In this article, an overview of the prevalence, severity, and risk factors for heart failure in maintenance dialysis patients is provided and the diagnosis of heart failure in these patients is revisited.” (A. Y. M. Wang, aymwang@hku.hk)

>>>PNN NewsWatch
* Injectable terbutaline should not be used for prevention or prolonged treatment (more than 48–72 hours) of preterm labor, FDA cautioned yesterday. A boxed warning and contraindication are being added to product labeling about the possibility of serious maternal heart problems and death associated with this use and route of administration of the drug.
* Lot number 284081 of
Upsher-Smith’s Jantoven Warfarin Sodium Tablets 3 mg is being recalled after one bottle was found to contain 10-mg tablets.
*
“Prescription Drug Overdoses: An American Epidemic” is the topic of a CDC Public Health Grand Rounds presented live yesterday and archived on the agency’s website. Continuing pharmacy education credit is available for the program, which describes a 5-fold increase in prescription drug–related deaths since 1990 and a parallel 10-fold increase in use of opioid analgesics.
* Just three endemic countries remain in the fight to eradicate
Guinea worm disease, former President Jimmy Carter said at a press briefing on Thursday. “Guinea worm disease is fewer than 1,800 cases away from becoming only the second disease in history to be wiped from Earth,” said Carter, who was joined by officials from Niger and Nigeria at the Carter Center in Atlanta to recognize successes with eradication in those African nations. Of the 1,800 remaining cases, 94% are in southern Sudan, and pockets of the disease are also found in eastern Mali and western Ethiopia.
*
PNN will not be published on Mon., Feb. 21, Presidents Day.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Feb. 22, 2011 * Vol. 18, No. 35
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Feb. 19 issue of Lancet (2011; 377).
Beclomethasone in Mild Persistent Asthma: Inhaled corticosteroids may be useful as rescue therapy in children with mild persistent asthma, according to results of the TREXA trial (pp. 650–7). Investigators conclude that daily inhaled corticosteroids are the most effective therapy for this condition. They add that rescue albuterol should not be used, based on these findings from a 44-week comparison of beclomethasone, albuterol, and placebo: “843 children and adolescents were enrolled into this trial, of whom 288 were assigned to one of four treatment groups; combined (n =71), daily beclomethasone (n = 72), rescue beclomethasone (n = 71), and placebo (n = 74)—555 individuals were excluded during the run-in, according to predefined criteria. Compared with the placebo group (49%, 95% CI 37–61), the frequency of exacerbations was lower in the daily (28%, 18–40, p = 0.03), combined (31%, 21–43, p = 0.07), and rescue (35%, 24–47, p = 0.07) groups. Frequency of treatment failure was 23% (95% CI 14–43) in the placebo group, compared with 5.6% (1.6–14) in the combined (p = 0.012), 2.8% (0–10) in the daily (p = 0.009), and 8.5% (2–15) in the rescue (p = 0.024) groups. Compared with the placebo group, linear growth was 1.1 cm (SD 0.3) less in the combined and daily arms (p < 0.0001), but not the rescue group (p = 0.26). Only two individuals had severe adverse events; one in the daily beclomethasone group had viral meningitis and one in the combined group had bronchitis.” (F. D. Martinez, fernando@arc.arizona.edu)
Genes & Parkinson’s Disease: A meta-analysis of five genome-wide association studies for Parkinson’s disease show these links between loci, including MAPT and SNCA, and patients’ risk of Parkinson’s disease (pp. 641–9): “We identified 11 loci that surpassed the threshold for genome-wide significance (p < 5 × 10−8). Six were previously identified loci (MAPT, SNCA, HLA-DRB5, BST1, GAK, and LRRK2) and five were newly identified loci (ACMSD, STK39, MCCC1/LAMP3, SYT11, and CCDC62/HIP1R). The combined population-attributable risk was 60.3% (95% CI 43.7–69.3). In the risk-profile analysis, the odds ratio in the highest quintile of disease risk was 2.51 (95% CI 2.23–2.83) compared with 1.00 in the lowest quintile of disease risk.” (A. Singleton, singleta@mail.nih.gov)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2011; 342).
Elevated Blood Pressure in Adolescents: Increases in diastolic blood pressures among Swedish men examined for military service were more strongly associated with mortality than elevated systolic blood pressures, researchers report (d643). Of 1.2 million men with a mean age of 18.4 years and examined between 1969 and 1995, these patterns were observed during a median of 24 years of follow-up: “28,934 (2.4%) men died. The relation of systolic blood pressure to total mortality was U shaped, with the lowest risk at a systolic blood pressure of about 130 mm Hg. This pattern was driven by the relation to non-cardiovascular mortality, whereas the relation to cardiovascular mortality was monotonically increasing (higher risk with higher blood pressure). The relation of diastolic blood pressure to mortality risk was monotonically increasing and stronger than that of systolic blood pressure, in terms of both relative risk and population attributable fraction (deaths that could be avoided if blood pressure was in the optimal range). Relations to cardiovascular and non-cardiovascular mortality were similar, with an apparent risk threshold at a diastolic blood pressure of about 90 mm Hg, below which diastolic blood pressure and mortality were unrelated, and above which risk increased steeply with higher diastolic blood pressures.” (J. Sundström, johan.sundstrom@medsci.uu.se)

>>>PNN JournalWatch
* Cysteine: A Potential Biomarker for Obstructive Sleep Apnea, in Chest, 2011; 139: 246–52. (F. Cintra, fatimacintra@interair.com.br)
* Pulmonary Complications of Lung Transplantation, in
Chest, 2011; 139: 402–11. (S. Nathan, steven.nathan@inova.org)
* Gastric Epithelial Stem Cells, in
Gastroenterology, 2011; 140: 412–24. (J. C. Mills, jmills@wustl.edu)
* Histamine-2 Receptor Antagonist Use and Incident Dementia in an Older Cohort, in
Journal of the American Geriatrics Society, 2011; 59: 251–7. (S. Gray, slgray@u.washington.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Feb. 23, 2011 * Vol. 18, No. 36
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Early-release article and Feb. 23 issue of JAMA (2011; 305).
Preserving Power of Antimicrobial Agents: Writing that antibiotic resistance represents a “a growing global public health threat,” the author of a Commentary issues a call for action (doi: 10.1001/jama.2011.279): “Health care professionals from across the medical and veterinary communities can play a critical role in addressing the resistance problem, from prescribing antimicrobial agents appropriately to raising awareness among political leaders and helping to put a human face on this public health threat.…
“The stakes could not be higher. Without action, deaths and morbidity from antimicrobial resistance will continue to increase and the drug development pipeline will run dry. There is a moral obligation to patients and to the nation to prevent the unthinkable outcome of a return to the preantibiotic era and to ensure that these precious resources are available for future generations.” (J. M. Hughes,
jmhughe@emory.edu)
Fractures with Bisphosphonates: Older women treated with bisphosphonates for more than 5 years have a significantly increased risk of subtrochanteric or femoral shaft fractures, a study shows (pp. 783–9). The absolute risk of fracture is low, as noted in these results from an Ontario case–control study of 205,466 patients starting bisphosphonate therapy in 2002–08: “We identified 716 women who sustained a subtrochanteric or femoral shaft fracture following initiation of bisphosphonate therapy and 9,723 women who sustained a typical osteoporotic fracture of the intertrochanteric region or femoral neck. Compared with transient bisphosphonate use, treatment for 5 years or longer was associated with an increased risk of subtrochanteric or femoral shaft fracture (adjusted odds ratio, 2.74; 95% confidence interval, 1.25–6.02). A reduced risk of typical osteoporotic fractures occurred among women with more than 5 years of bisphosphonate therapy (adjusted odds ratio, 0.76; 95% confidence interval, 0.63–0.93). Among 52,595 women with at least 5 years of bisphosphonate therapy, a subtrochanteric or femoral shaft fracture occurred in 71 (0.13%) during the subsequent year and 117 (0.22%) within 2 years.” (L. Y. Park-Wyllie, parkwylliel@smh.ca)
Nitroglycerin & BMD: Bone mineral density was modestly increased among postmenopausal women who used nitroglycerin ointment 15 mg/d at bedtime for 24 months, researchers report (pp. 800–07): “At 2 years, women randomized to the nitroglycerin group had significant increases in areal BMD at the lumbar spine (from 1.05 to 1.14 g/cm2 vs placebo from 1.06 to 1.08 g/cm2; percentage change, 6.7%; 95% confidence interval [CI], 5.2%–8.2%; P < .001); total hip (from 0.92 to 0.97 g/cm2 vs placebo from 0.93 to 0.92 g/cm2; 6.2%; 95% CI, 5.6%–7.0%; P < .001); and femoral neck (from 0.88 to 0.93 g/cm2 vs placebo from 0.87 to 0.86 g/cm2; 7.0%; 95% CI, 5.5%-8.5%; P < .001). At 2 years, nitroglycerin also increased volumetric trabecular BMD (11.9% and 8.5%), cortical thickness (13.9% and 24.6%), periosteal circumference (7.4% and 2.9%), polar section modulus (10.7% and 9.8%), and polar moment of inertia (7.3% and 14.5%) at the radius and tibia, respectively (all P < .001); and increased bone-specific alkaline phosphatase by 34.8% and decreased urine N-telopeptide by 54.0% (P < .001).” (S. A. Jamal, sophie.jamal@utoronto.ca)
While these results differ from those of a prior trial, “an adequately powered, larger study using nitroglycerin ointment with fracture as an outcome” should be conducted, an editorialist concludes (
pp. 826–7): “If such a study demonstrates efficacy for reducing fractures, clinicians would have a novel and inexpensive therapy for osteoporosis. The findings of the current study also should prompt development of additional nitric oxide donors with greater skeletal efficacy and a better adverse effect profile, particularly with regard to headaches.” (S. Khosla, khosla.sundeep@mayo.edu)

>>>PNN NewsWatch
* FDA has updated the Pregnancy section of drug labels for the entire class of antipsychotic drugs to provide more and consistent information about the potential risk for extrapyramidal signs and withdrawal symptoms (agitation, changes in muscle tone, tremor, sleepiness, difficulty with breathing or feeding) in newborns whose mothers were treated with these drugs during the third trimester of pregnancy.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Feb. 24, 2011 * Vol. 18, No. 37
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Feb. 24 issue of the New England Journal of Medicine (2011; 364).
Farms & Asthma: Exposure to a wide variety of microbes on farms provides children growing up there with protection against asthma, a study confirms (pp. 701–9). Two cross-sectional studies, PARSIFAL (Prevention of Allergy—Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle) and GABRIELA (Multidisciplinary Study to Identify the Genetic and Environmental Causes of Asthma in the European Community Advanced Study), examined dust on mattresses and in children’s rooms for bacteria and fungi, with these results: “In both studies, children who lived on farms had lower prevalences of asthma and atopy and were exposed to a greater variety of environmental microorganisms than the children in the reference group. In turn, diversity of microbial exposure was inversely related to the risk of asthma (odds ratio for PARSIFAL, 0.62; 95% confidence interval [CI], 0.44 to 0.89; odds ratio for GABRIELA, 0.86; 95% CI, 0.75 to 0.99). In addition, the presence of certain more circumscribed exposures was also inversely related to the risk of asthma; this included exposure to species in the fungal taxon eurotium (adjusted odds ratio, 0.37; 95% CI, 0.18 to 0.76) and to a variety of bacterial species, including Listeria monocytogenes, bacillus species, corynebacterium species, and others (adjusted odds ratio, 0.57; 95% CI, 0.38 to 0.86).” (M. J. Ege, markus.ege@med.uni-muenchen.de)
While attributing better health of children on farms to fresh air, exercise, and sunlight is attractive, an editorialist notes surprise that it’s the microbes that reduce the incidence of asthma and atopy in this group (
pp. 769–70). This finding has important implications for prevention, he adds: “In the past 30 years, the prevalence of childhood asthma has more than doubled, and although the treatments used to control asthma have improved greatly, there has been little progress in prevention. Identification of the association between exposure to an environment rich in nonpathogenic microbes and reduced risk of asthma offers hope that this and other new conceptual breakthroughs will lead to novel preventive strategies. These findings also raise additional questions about the possible mechanisms through which the nature and range of microbial exposure may alter the developmental biology of the lung and immune system. Resolving these questions is of critical importance if we are to bring the substantial health benefits of being raised on a farm to those who are not.” (J. E. Gern)
BMI & Mortality in Asians: For body mass index, the range of desirable values is different in Asians than those of European descent, and underweight is a more consistent risk factor for increased risk of mortality, an analysis shows (pp. 719–29). Among 1.1 million people in 19 Asian cohorts, these associations were made based on 120,700 deaths during 9.2 years of follow-up: “In the cohorts of East Asians, including Chinese, Japanese, and Koreans, the lowest risk of death was seen among persons with a BMI (the weight in kilograms divided by the square of the height in meters) in the range of 22.6 to 27.5. The risk was elevated among persons with BMI levels either higher or lower than that range—by a factor of up to 1.5 among those with a BMI of more than 35.0 and by a factor of 2.8 among those with a BMI of 15.0 or less. A similar U-shaped association was seen between BMI and the risks of death from cancer, from cardiovascular diseases, and from other causes. In the cohorts comprising Indians and Bangladeshis, the risks of death from any cause and from causes other than cancer or cardiovascular disease were increased among persons with a BMI of 20.0 or less, as compared with those with a BMI of 22.6 to 25.0, whereas there was no excess risk of either death from any cause or cause-specific death associated with a high BMI.” (W. Zheng, wei.zheng@vanderbilt.edu)
Transforming Graduate Medical Education: “New perspectives and skills for evidence-based practice, effective use of information technology, quality measurement and improvement, cost awareness, care coordination, leadership of interdisciplinary teams, and shared decision making” are among the skills needed by future physicians, write authors from the Medicare Payment Advisory Commission, which provides supplemental payments to hospitals with residents (pp. 693–5; G. Hackbarth).

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Feb. 25, 2011 * Vol. 18, No. 38
Providing news and information about medications and their proper use

>>>Medical Care Highlights
Source:
Feb. and Mar. issues of Medical Care (2011; 49).
Diagnosis, Service Utilization & Medical Homes: In a study that provides lessons for medication therapy management programs, researchers find that a diagnosis of a chronic condition is not an adequate predictor of patients’ use of heath care services (pp. 149–55). Among a population of working-age adults, 52% had chronic health care needs. Those who needed help with activities of daily livings (ADLs) or instrumental ADLs (IADLs) had more acute and chronic conditions, the highest utilization rates of services, the greatest number of acute and chronic conditions, and more difficulties with access to medical and prescription services, especially when they reported periods of being uninsured. Those with ADL/IADL limitations made up less than 10% of the entire study population, but their care cost $100 billion, more than what was spent on everyone else. Asking “if we build [the medical home], who will come,” the authors conclude, “These data reveal the drawbacks of selecting the potential population targeted for a medical home on the basis of diagnosis alone. New measurement approaches on the basis of shared need for ongoing health and related services are required to bridge the division between disability and chronic health conditions.” (S. P. Gulley, gulley@brandeis.edu)
Physician Test Scores & Antibiotic Prescribing: Women physicians, but not their male counterparts, with better clinical and communication skills are less likely to prescribe antibiotics for viral respiratory infections (VRIs), researchers report (pp. 156–65). Antibiotic prescriptions written in 1993–2007 by 442 Quebec general practitioners and pediatricians and dispensed within 7 days of a VRI visit showed these patterns in relation participants’ scores on the Canadian clinical skills examination (CSE) in 1993–96: “Better clinical and communication skills were associated with a reduction in the risk of antibiotic prescribing, but only for female physicians. Every 1-standard deviation increase in CSE score was associated with a 19% reduction in the risk of antibiotic prescribing (risk ratio, 0.81; 95% confidence interval, 0.68–0.97). Better clinical skills were associated with an even greater reduction in risk among female physicians with higher workloads (risk ratio, 0.48; 95% confidence interval, 0.29–0.79). (G. Cadieux, genevieve.cadieux@mail.mcgill.ca)
Adherence to Fracture-Preventive Meds: Patients’ perceived need for medications for fracture prevention affected their adherence in a study and survey of 1,155 patients (pp. 273–80): “Trust in the prescribing physician, prevalent vertebral fracture on spine imaging, patients’ self-reported susceptibility to and perceived severity of fractures, and medication concerns were independently associated with perceived need for medication. Bone mineral density and fracture history were only weakly associated with perceived need for medication. Trust in the physician was associated with perceived severity of fractures but not with self-reported susceptibility to fractures. Patients’ perceptions that their physician communicates openly with them and their satisfaction with their physician’s decision-making style are strongly associated with their trust in that physician.” (J. T. Schousboe, scho0600@umn.edu)
Manuscripts Sought: Medical Care will publish a special issue featuring clinical and health policy research advances related to medication prescribing and use, the editors announce (online only). Authors should send a letter of intent by Mar. 30, and manuscripts should be submitted by July 31 for the Dr. Frances Kelsey Special Issue on “Pharmaceuticals and the Health of the Public.” (S. Houchin, medicalcare@comcast.net)

>>>PNN NewsWatch
* FDA and Georgetown U. Medical Center yesterday announced a partnership to stimulate innovation in regulatory science, ethics, education, and training. The agreement between the two Washington, DC–based institutions involves joint research and public health activities in areas such as novel technologies, public health preparedness, ethics, and bioinformatics; joint mentorship of doctoral and postdoctoral students in collaborative research; scientific staff exchanges and professional development opportunities; and shared access to and development of important training and continuing education activities.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Feb. 28, 2011 * Vol. 18, No. 39
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Feb. 26 issue of Lancet (2011; 377).
Belimumab in SLE: In 865 patients with systemic lupus erythematosus, belimumab significantly improved activity-index scores without an increase in serious adverse events over those seen with placebo, researchers report (pp. 721–31). Efficacy of the monoclonal antibody, which inhibits B-lymphocyte stimulator, was measured using a primary efficacy endpoint of improvement in the Systemic Lupus Erythematosus Responder Index (SRI) at week 52 (reduction ≥4 points in SELENA-SLEDAI score; no new British Isles Lupus Assessment Group [BILAG] A organ domain score and no more than 1 new B organ domain score; and no worsening [<0.3 increase] in Physician’s Global Assessment [PGA] score) versus baseline: “Significantly higher SRI rates were noted with belimumab 1 mg/kg (148 [51%], odds ratio 1.55 [95% CI 1.10–2.19]; p = 0.0129) and 10 mg/kg (167 [58%], 1.83 [1.30–2.59]; p = 0.0006) than with placebo (125 [44%]) at week 52. More patients had their SELENA-SLEDAI score reduced by at least 4 points during 52 weeks with belimumab 1 mg/kg (153 [53%], 1.51 [1.07–2.14]; p = 0.0189) and 10 mg/kg (169 [58%], 1.71 [1.21–2.41]; p = 0.0024) than with placebo (132 [46%]). More patients given belimumab 1 mg/kg (226 [78%], 1.38 [0.93—2.04]; p = 0.1064) and 10 mg/kg (236 [81%], 1.62 [1.09–2.42]; p = 0.0181) had no new BILAG A or no more than 1 new B flare than did those in the placebo group (210 [73%]). No worsening in PGA score was noted in more patients with belimumab 1 mg/kg (227 [79%], 1.68 [1.15–2.47]; p = 0.0078) and 10 mg/kg (231 [80%], 1.74 [1.18–2.55]; p = 0.0048) than with placebo (199 [69%]).” (M. A. Petri, mpetri@jhmi.edu)
Candesartan in Stroke: Careful lowering of blood pressure in 2,029 patients with acute ischemic or hemorrhagic stroke with candesartan provided no benefits and was potentially harmful, report investigators from the SCAST trial (pp. 741–50). A composite endpoint of vascular death, myocardial infarction, or stroke during the first 6 months was not significantly different between those receiving candesartan versus placebo. Functional outcomes were poorer with the angiotensin II receptor blocker, although not significantly so at the P < .025 level. (E. C. Sandset, eivind.berge@medisin.uio.no)
Cell-Cultured Influenza Vaccine: A trivalent influenza vaccine made using cell-culture technology was efficacious and safe, with protection afforded at similar antibody titers as with egg-derived products, according to a Phase III trial conducted in the U.S. (pp. 751–9). Among 7,250 participants, these results were noted: “Overall protective efficacy for antigenically matched influenza infection was 78.5% (95% CI 60.8–88.2). The vaccine was well tolerated with no treatment-related serious adverse events. Adverse events were mainly mild and transient. An HI titre of at least 1:15 provided a reliable correlate of cell-culture-derived influenza vaccine-induced protection; no additional benefit was noted with titres greater than 1:30.” (P. N. Barrett, noel_barrett@baxter.com)
MI Triggers: Air pollution is an important trigger of myocardial infarction, a study shows, one made even more important by the widespread exposure of people to it, investigators maintain (pp. 732–40). Cocaine use carries the highest odds ratio but the lowest exposure rate of several triggers assessed in a comparative risk meta-regression of studies. Other drug-related triggers are marijuana smoking and coffee or alcohol consumption. (T. S. Nawrot, tim.nawrot@uhasselt.be)

>>>PNN NewsWatch
* Azilsartan medoxomil (Edarbi, Takeda) was approved on Friday by FDA for treatment of hypertension in adults. Data from clinical studies showed this angiotensin II receptor blocker to be more effective in lowering 24-hour blood pressure than two other FDA-approved ARBs, valsartan and olmesartan.

>>>PNN JournalWatch
* Drinking: Messages for the Beer Mat, in BMJ, 2011; 342: d1231. (J. Smith, jsmith@bmj.com)
* Performance-Based Payment Incentives Increase Burden and Blame for Hospital Nurses, in
Health Affairs, 2011; 30: 211–8. (E. T. Kurtzman, sonetk@gwumc.edu)
* The Great Debate: Medicine or Surgery—What is Best for the Patient with Type 2 Diabetes?, in
Diabetes Care, 2011; 34: 763–70. (A.. B. Goldfine, allison.goldfine@joslin.harvard.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 1, 2011 * Vol. 18, No. 40
Providing news and information about medications and their proper use

>>>Internal Medicine Report I
Source:
Mar. 1 issue of the Annals of Internal Medicine (2011; 154).
Steroid Therapy of Rhinosinusitis: Polyp size was reduced and olfaction improved by a course of oral steroids followed by topical steroids in a 6-month study of 60 adults with chronic rhinosinusitis (CRS) and nasal polyposis (pp. 293–302). Treatment consisted of oral prednisolone 25 mg/d, or placebo for 2 weeks, followed by fluticasone propionate nasal drops 400 µg twice daily for 8 weeks and then fluticasone propionate nasal spray 200 µg twice daily for 18 weeks. Results showed: “The mean decrease in polyp grade from baseline to 2 weeks was 2.1 units (SD, 1.1) in the prednisolone group and 0.1 unit (SD, 1.0) in the placebo group (mean difference between groups, −1.8 units [95% CI, −2.4 to −1.2 units]; P < 0.001). The difference between groups was −1.08 units (CI, −1.74 to −0.42 unit; P = 0.001) at 10 weeks and −0.8 unit (CI, −1.8 to 0.2 unit; P = 0.11) at 28 weeks. The mean decrease in hyposmia score from baseline to 2 weeks was 31.12 mm (SD, 30.1) in the prednisolone group and 1.41 mm (SD, 30.6) in the placebo group (mean difference between groups, −28.33 mm [CI, −42.71 to −13.96 mm]; P = 0.002). The difference between groups was −16.06 mm (CI, −30.99 to −1.13 mm; P = 0.03) at 10 weeks and −12.13 mm (CI, −30.55 to 6.29 mm; P = 0.19) at 28 weeks. Prednisolone therapy resulted in transient suppression of adrenal function and increase in bone turnover after 2 weeks, with a return to baseline at 10 and 28 weeks.” (S. Vaidyanathan)
While welcoming these findings, editorialists caution (
pp. 365–7): “Clinicians must temper their enthusiasm for oral therapy with recognition of potential systemic adverse effects on the [hypothalamic–pituitary–adrenal] axis and bone metabolism. These adverse effects are likely to be greatest among elderly patients, postmenopausal women, and those who receive repeated courses of oral therapy. Thus, we believe that oral steroid therapy should be initiated only when patients with chronic rhinosinusitis with nasal polyps have an unsatisfactory response to at least 3 months of treatment with intranasal corticosteroids. We advocate an initial daily dose of 0.5 to 1 mg/kg that is tapered after 2 weeks, followed by intranasal corticosteroid therapy.” (J. Mullol, jmullol@clinic.ub.es)

>>>Internal Medicine Report II
Source:
Feb. 28 issue of the Archives of Internal Medicine (2011; 171).
Complex Prescription Drug Regimens: Standardized instructions are needed for prescription medications, a study shows, especially when patients are trying to simplify and safely use complex regimens (pp. 300–5). Based on structured interviews of 464 adults ages 55 to 74 years who were asked to organize a hypothetical 7-drug regimen, the investigators determined: “Participants on average identified 6 times (SD, 1.8 times; range, 3–14 times) in 24 hours to take the 7 drugs. One-third of the participants (29.3%) dosed their medications 7 or more times per day, while only 14.9% organized the regimen into 4 or fewer times a day. In multivariable analysis, low literacy was an independent predictor of more times per day for dosing the regimen (beta = 0.67; 95% confidence interval, 0.12–1.22; P = .02). Instructions for 2 of the drugs were identical, yet 31.0% of the participants did not take these medications at the same time. Another set of drugs had similar instructions, with the primary exception of 1 drug having the added instruction to take ‘with food and water.’ Half of the participants (49.5%) took these medications at different times. When the medications had variable expressions of the same dose frequency (eg, ‘every 12 hours’ vs ‘twice daily&rsquoWinking, 79.0% of the participants did not consolidate the medications.” (M. S. Wolf, mswolf@northwestern.edu)
When Metformin Fails in Type 2 Diabetes: In patients with type 2 diabetes who do not achieve the 7% target for A1C levels, sulfonylureas and basal insulin are the best-validated options, researchers report (pp. 365–6). Overall, published data show that 55% and 51% of patients on these respective agents achieve the 7% A1C level. In a less-validated tier of alternative agents, glucagon-like peptide 1 agonists enabled the highest proportion of patients (47%) to reach the target level, followed by glinides (41%), glitazones (40%), dipeptidyl peptidase 4 inhibitors (39%), and alpha-glucosidase inhibitors (19%). (D. Giugliano, dario.giugliano@unina2.it)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 2, 2011 * Vol. 18, No. 41
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Mar. 2 issue of JAMA (2011; 305).
Genes & Diabetes: People of white European descent who have variants of the HMGA1 gene are at increased risk of developing type 2 diabetes, researchers report (pp. 903–12). In a case–control study of nearly 9,000 people in Italy, the U.S., and France, these patterns were found: “The most frequent functional HMGA1 variant, IVS5-13insC, was present in 7% to 8% of patients with type 2 DM in all 3 populations. The prevalence of IVS5-13insC variant was higher among patients with type 2 DM than among controls in the Italian population (7.23% vs 0.43% in one control group; OR, 15.77 [95% confidence interval {CI}, 8.57-29.03]; P < .001 and 7.23% vs 3.32% in the other control group; OR, 2.03 [95% CI, 1.51-3.43]; P < .001). In the US population, the prevalence of IVS5-13insC variant was 7.7% among patients with type 2 DM vs 4.7% among controls (OR, 1.64 [95% CI, 1.05-2.57]; P = .03). In the French population, the prevalence of IVS5-13insC variant was 7.6% among patients with type 2 DM and 0% among controls (P = .046). In the Italian population, 3 other functional variants were observed. When all 4 variants were analyzed, HMGA1 defects were present in 9.8% of Italian patients with type 2 DM and 0.6% of controls. In addition to the IVS5 C-insertion, the c.310G>T (p.E104X) variant was found in 14 patients and no controls (Bonferroni-adjusted P = .01); the c.*82G>A variant (rs2780219) was found in 46 patients and 5 controls (Bonferroni-adjusted P < .001); the c.*369del variant was found in 24 patients and no controls (Bonferroni-adjusted P < .001).” (A. Brunetti, brunetti@unicz.it)
An editorialist links genetic findings with success of therapy with various antidiabetic agents (
pp. 938–9): “This information may lead to targeted therapies for various subtypes of type 2 DM. For instance, common variants near the ataxia telangiectasia mutated gene were recently associated with treatment success with metformin. Similarly, patients with type 2 DM who were harboring the p.Glu23Lys polymorphism in the potassium inwardly-rectifying channel (subfamily J, member 11) gene were more likely to develop secondary failures to sulfonylurea therapy. It is anticipated that the discoveries of novel loci such as HMGA1 will soon be translated into therapeutic decision making, and thereby improve the health of patients with type 2 DM.” (A. Garg, abhimanyu.garg@utsouthwestern.edu)
Antihypertensive Therapy for Preventing Events in Patients Without Hypertension: Cardiovascular events and all-cause mortality are decreased when antihypertensive agents are used to treat patients without clinically defined hypertension who have diabetes or prior cardiovascular disease, a review of 25 articles shows (pp. 913–22): “Compared with controls, participants receiving antihypertensive medications had a pooled relative risk of 0.77 (95% confidence interval [CI], 0.61 to 0.98) for stroke, 0.80 (95% CI, 0.69 to 0.93) for MI, 0.71 (95% CI, 0.65 to 0.77) for CHF, 0.85 (95% CI, 0.80 to 0.90) for composite CVD events, 0.83 (95% CI, 0.69 to 0.99) for CVD mortality, and 0.87 (95% CI, 0.80 to 0.95) for all-cause mortality from random-effects models. The corresponding absolute risk reductions per 1,000 persons were −7.7 (95% CI, −15.2 to −0.3) for stroke, −13.3 (95% CI, −28.4 to 1.7) for MI, −43.6 (95% CI, −65.2 to −22.0) for CHF events, −27.1 (95% CI, −40.3 to −13.9) for composite CVD events, −15.4 (95% CI, −32.5 to 1.7) for CVD mortality, and −13.7 (95% CI, −24.6 to −2.8) for all-cause mortality.” (L. A. Bazzano, lbazzano@tulane.edu)

>>>PNN NewsWatch
* FDA yesterday approved roflumilast (Daliresp, Forest) for reducing the risk of chronic obstructive pulmonary disease (COPD) exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. An inhibitor of phosphodiesterase type 4, roflumilast is not intended to treat primary emphysema. In clinical trials, oral roflumilast 500 mcg once daily significantly reduced the rate of moderate or severe exacerbations, compared with placebo, with decreases of 15% to 18%. The most common adverse reactions were diarrhea, weight decrease, nausea, headache, back pain, influenza, insomnia, dizziness, and decreased appetite.
*
Abacavir use is not associated with increased risk of myocardial infarction, FDA has concluded.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 3, 2011 * Vol. 18, No. 42
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Mar. 3 issue of the New England Journal of Medicine (2011; 364).
Dosing Patterns for Loop Diuretics: Whether administered in low or high doses, or by bolus or continuous infusion, loop diuretics have similar but possibly different effects in patients with acute decompensated heart failure, report researchers from the Diuretic Optimization Strategies Evaluation (DOSE) trial (pp. 797–805). Furosemide was administered either I.V. every 12 hours or continuously and at a dose equivalent to either the patient’s prior oral dose or 2.5 times that much. In 308 patients, these changes resulted based on coprimary end points of patients’ global assessment of symptoms (quantified as the area under the curve [AUC] of the score on a visual-analogue scale over 72 hours) and the change in the serum creatinine level from baseline to 72 hours: “In the comparison of bolus with continuous infusion, there was no significant difference in patients’ global assessment of symptoms (mean AUC, 4,236 ± 1,440 and 4,373 ± 1,404, respectively; P = 0.47) or in the mean change in the creatinine level (0.05 ± 0.3 mg per deciliter [4.4 ± 26.5 µmol per liter] and 0.07 ± 0.3 mg per deciliter [6.2 ± 26.5 µmol per liter], respectively; P = 0.45). In the comparison of the high-dose strategy with the low-dose strategy, there was a nonsignificant trend toward greater improvement in patients’ global assessment of symptoms in the high-dose group (mean AUC, 4,430 ± 1,401 vs. 4,171 ± 1,436; P = 0.06). There was no significant difference between these groups in the mean change in the creatinine level (0.08 ± 0.3 mg per deciliter [7.1 ± 26.5 µmol per liter] with the high-dose strategy and 0.04±0.3 mg per deciliter [3.5 ± 26.5 µmol per liter] with the low-dose strategy, P = 0.21). The high-dose strategy was associated with greater diuresis and more favorable outcomes in some secondary measures but also with transient worsening of renal function.” (G. M. Felker, michael.felker@duke.edu)
DOSE introduces comparative effectiveness research into diuretic therapy, an editorialist writes, and has these implications for therapy (
pp. 877–8): “The DOSE trial has importantly identified a lack of greater benefit with the diuretic regimen of continuous infusion—a regimen that is used frequently—than with a regimen of intermittent boluses. It also showed that, despite theoretical concerns and the findings of prior observational studies, a high dose of loop diuretics, as compared with a low dose, did not substantially worsen renal function. Both of these findings should change current practice. Since a high-dose regimen may relieve dyspnea more quickly without adverse effects on renal function, that regimen is preferable to a low-dose regimen. Administration of boluses may be more convenient than continuous infusion and equally effective.” (G. C. Fonarow)
Apixaban in Atrial Fibrillation: The factor Xa inhibitor apixaban provided a useful substitute in patients with atrial fibrillation intolerant of warfarin, the AVERROES (Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment) study shows (pp. 806–17). Apixaban 5 mg twice daily or aspirin 81–324 mg/d produced these results in 5,599 study participants: “There were 51 primary outcome events (1.6% per year) among patients assigned to apixaban and 113 (3.7% per year) among those assigned to aspirin (hazard ratio with apixaban, 0.45; 95% confidence interval [CI], 0.32 to 0.62; P < 0.001). The rates of death were 3.5% per year in the apixaban group and 4.4% per year in the aspirin group (hazard ratio, 0.79; 95% CI, 0.62 to 1.02; P = 0.07). There were 44 cases of major bleeding (1.4% per year) in the apixaban group and 39 (1.2% per year) in the aspirin group (hazard ratio with apixaban, 1.13; 95% CI, 0.74 to 1.75; P = 0.57); there were 11 cases of intracranial bleeding with apixaban and 13 with aspirin. The risk of a first hospitalization for cardiovascular causes was reduced with apixaban as compared with aspirin (12.6% per year vs. 15.9% per year, P < 0.001). The treatment effects were consistent among important subgroups.” (S. J. Connolly, stuart.connolly@phri.ca)

>>>PNN NewsWatch
* FDA moved yesterday to force removal of some 500 prescription cough, cold, and allergy products from the U.S. market. All are unapproved DESI products, and most have been used rarely in recent decades.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 4, 2011 * Vol. 18, No. 43
Providing news and information about medications and their proper use

>>>Pharmacotherapy Report
Source:
Mar. issue of Pharmacotherapy (2011; 31).
Genotype in H. pylori Eradication: Rapid cytochrome P450 2C19 metabolizers may require higher doses of omeprazole to achieve eradication of Helicobacter pylori, based on results of a study of 128 adults in Taiwan (pp. 227–38). Participants had H. pylori–positive duodenal ulcers and were treated with one of four combinations of omeprazole and amoxicillin (O1 and O2 denoted omeprazole 20 mg once or twice daily, respectively; A1 and A2 denoted amoxicillin 250 or 500 mg, respectively, four times daily). Results showed: “The intent-to-treat cure rates (95% confidence interval [CI]) in groups O2A2, O2A1, O1A2, and O1A1 were 76% (95% CI 59–87%), 72% (95% CI 54–84%), 50% (95% CI 34–66%) and 52% (95% CI 35–68%), respectively. Eradication of H. pylori infection was statistically significantly dependent on omeprazole dosage, CYP2C19 genotype, age, gastritis status, and H. pylori density. All CYP2C19 poor metabolizers were cured, whereas the H. pylori cure rate in CYP2C19 extensive metabolizers varied from 44–76% in the different treatment groups. Eradication of H. pylori was favored in the omeprazole higher dose groups versus the lower dose groups (79% vs 53%, p = 0.004). No secondary antibiotic resistance was found. Thirty-seven (95%) of 39 patients who failed with the initial treatment were cured by subsequent antibiotic susceptibility–driven proton pump inhibitor–based triple therapy.” (C-J Lin, clementumich@ntu.edu.tw)
Hospitalizations & H. pylori Eradication: Hospitalizations for major gastrointestinal ulcers are reduced in the 6 months after administration of Helicobacter pylori eradication therapy following a diagnosis of ulcers, according to a second study from Taiwan (pp. 239–47). Among 838,176 patients who received H. pylori eradication therapy or antisecretory therapy alone in 2001–06, these patterns were noted: “Compared with the antisecretory therapy alone group, the H. pylori therapy group (initial users) had a significantly decreased risk of hospitalization for major ulcer events (adjusted hazard ratio [AHR] 0.57, 95% confidence interval [CI] 0.54–0.59, p < 0.001). However, later use of H. pylori therapy was associated with a higher risk of hospitalization for major ulcer events (time lag 181–365 days, AHR 1.68, 95% CI 1.51–1.86, p < 0.001; > 365 days, AHR 1.74, 95% CI 1.67–1.80, p < 0.001) compared with those who received H. pylori therapy within 6 months (≤ 180 days) after gastrointestinal ulcers were diagnosed.” (W-F Huang, huang@ym.edu.tw)
Nelfinavir–PPI Interactions in HIV: Clinicians should be careful about using proton-pump inhibitors in patients with HIV who are on nelfinavir-based regimens, researchers conclude (pp. 253–61). Retrospective cohort data from an integrated health system in northern California show that PPI use should be minimized in those who have achieved undetectable viral levels with nelfinavir, and that use of the PPIs should be limited to 30 days if the agents are needed: “The use of PPIs had little effect on the ability to achieve an undetectable HIV viral load (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.58–1.19, p = 0.29), but there was an approximate 50% increased risk of virologic rebound with the concurrent use of PPIs (adjusted HR 1.53, 95% CI 1.06–2.19, p = 0.02). Short-term use of PPIs (defined as within 30 days of initial PPI dispensation) was not associated with increased risk of virologic rebound (HR 1.07, 95% CI 0.26–4.41, p = 0.93) compared with no use of PPIs.” (P. Saberi, parya.saberi@ucsf.edu)

>>>PNN NewsWatch
* Hypomagnesemia is a potential adverse result of long-term use of proton-pump inhibitors, FDA warned this week. Use of prescription PPIs for more than 1 year can lower serum magnesium levels, and magnesium supplementation fails to reverse the problem in about one-quarter of affected patients. FDA recommended baseline magnesium levels in patients starting long-term PPI treatment or when patients start therapy when already taking medications known to reduce serum magnesium levels (e.g., digoxin, diuretics). Symptoms of hypomagnesemia include tetany, arrhythmias, and convulsions, but many patients are asymptomatic. Treatment of PPI-induced hypomagnesemia can require discontinuance of the PPI if magnesium supplements are ineffective.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 7, 2011 * Vol. 18, No. 44
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Early-release article from BMJ (2011; 342).
Cannabis Use & Psychosis: Use of cannabis in adolescence increases the risk of developing psychoses, and continued use can increase the persistence of symptoms, researchers report (d738). In a study conducted among 1,923 individuals in Germany who were 14–24 years of age at baseline, a cohort study found these patterns at 3.5 (T2) and 8.4 (T3) years: “In individuals who had no reported lifetime psychotic symptoms and no reported lifetime cannabis use at baseline, incident cannabis use over the period from baseline to T2 increased the risk of later incident psychotic symptoms over the period from T2 to T3 (adjusted odds ratio 1.9, 95% confidence interval 1.1 to 3.1; P = 0.021). Furthermore, continued use of cannabis increased the risk of persistent psychotic symptoms over the period from T2 to T3 (2.2, 1.2 to 4.2; P = 0.016). The incidence rate of psychotic symptoms over the period from baseline to T2 was 31% (152) in exposed individuals versus 20% (284) in non-exposed individuals; over the period from T2 to T3 these rates were 14% (108) and 8% (49), respectively.” (J. van Os, j.vanos@sp.unimaas.nl)

>>>Lancet Highlights
Source:
Mar. 5 issue of Lancet (2011; 377).
Treating Bone Metastases in Castration-Resistant Prostate Cancer: In a study of 1,904 men with castration-resistant prostate cancer, denosumab proved better than zoledronic acid for preventing skeletal-related events (pp. 813–22). At 342 centers in 39 countries, patients received subcutaneous denosumab 120 mg or intravenous zoledronic acid every 4 weeks, with these results: “Median duration on study at primary analysis cutoff date was 12.2 months (IQR 5.9–18.5) for patients on denosumab and 11.2 months (IQR 5.6–17.4) for those on zoledronic acid. Median time to first on-study skeletal-related event was 20.7 months (95% CI 18.8–24.9) with denosumab compared with 17.1 months (15.0—19.4) with zoledronic acid (hazard ratio 0.82, 95% CI 0.71–0.95; p = 0.0002 for non-inferiority; p = 0.008 for superiority). Adverse events were recorded in 916 patients (97%) on denosumab and 918 patients (97%) on zoledronic acid, and serious adverse events were recorded in 594 patients (63%) on denosumab and 568 patients (60%) on zoledronic acid. More events of hypocalcaemia occurred in the denosumab group (121 [13%]) than in the zoledronic acid group (55 [6%]; p < 0.0001). Osteonecrosis of the jaw occurred infrequently (22 [2%] vs 12 [1%]; p = 0.09).” (K. Fizazi, fizazi@igr.fr)

>>>PNN NewsWatch
* Babies born to mothers who have taken topiramate during pregnancy are at increased risk of having cleft lip and palate, FDA warned on Friday. The risk of these birth defects is up to 3 times greater than with other antiepileptic agents (1.4% prevalence of oral clefts for babies exposed to topiramate during the first trimester, compared with 0.38% to 0.55% with other agents for seizures).
* Monthly liver enzyme tests are no longer required for those taking
ambrisentan (Letairis, Gilead), according to a modified warning box released on Friday by FDA. The agent was approved for treatment of pulmonary artery hypertension under provisions of a RiskMAP that focused on liver damage and fetal malformation. FDA now says the drug poses a low risk of liver injury.

>>>PNN JournalWatch
* Everolimus-Based, Calcineurin-Inhibitor-Free Regimen in Recipients of De-Novo Kidney Transplants: An Open-Label, Randomised, Controlled Trial, in Lancet, 2011; 377: 837–47. (K. Budde, klemens.budde@charite.de)
* COPD, Bone Metabolism, and Osteoporosis, in
Chest, 2011; 139:648–57. (W. Janssens, wim.janssens@uz.kuleuven.be)
* Occupational Asthma: Review of Assessment, Treatment, and Compensation, in
Chest, 2011; 139: 674–81. (C. T. Cowl, cowl.clayton@mayo.edu)
* Alternative Rehydration Methods: A Systematic Review and Lessons for Resource-Limited Care, in
Pediatrics, 2011; 127: e748–57. (S. Rouhani)
* Health Effects of Energy Drinks on Children, Adolescents, and Young Adults, in
Pediatrics, 2011; 127: 511–28. (S. M. Seifert)
* After GWAS: Searching for Genetic Risk for Schizophrenia and Bipolar Disorder, in
American Journal of Psychiatry, 2011; 168: 253–6. (E. S. Gershon)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 8, 2011 * Vol. 18, No. 45
Providing news and information about medications and their proper use

>>>Cardiology Highlights
Source:
Mar. 15 issue of the Journal of the American College of Cardiology (2011; 57).
Clopidogrel–Drug Interactions: Concerned clinicians have several options for avoiding drug interactions involving clopidogrel, authors of a review article conclude (pp. 1251–63): “Clopidogrel, a prodrug, requires hepatic cytochrome P450 (CYP) metabolic activation to produce the active metabolite that inhibits the platelet P2Y12 adenosine diphosphate (ADP) receptor, decreasing platelet activation and aggregation processes. Atorvastatin, omeprazole, and several other drugs have been shown in pharmacodynamic studies to competitively inhibit CYP activation of clopidogrel, reducing clopidogrel responsiveness. Conversely, other agents increase clopidogrel responsiveness by inducing CYP activity. The clinical implications of these pharmacodynamic interactions have raised concern because many of these drugs are coadministered to patients with coronary artery disease. There are multiple challenges in proving that a pharmacodynamic drug–drug interaction is clinically significant. To date, there is no consistent evidence that clopidogrel–drug interactions impact adverse cardiovascular events. Statins and proton pump inhibitors have been shown to decrease adverse clinical event rates and should not be withheld from patients with appropriate indications for therapy because of concern about potential clopidogrel–drug interactions. Clinicians concerned about clopidogrel–drug interactions have the option of prescribing either an alternative platelet P2Y12 receptor inhibitor without known drug interactions, or statin and gastro-protective agents that do not interfere with clopidogrel metabolism.” (E. R. Bates, ebates@umich.edu)
Triple Antiplatelet Therapy After Stent Implantation: Several benefits were evident when triple antiplatelet therapy was used in 499 patients undergoing long (30 mm or more) zotarolimus-eluting stent implantation, including decreased extent of late luminal loss, percent intimal hyperplasia volume, and angiographic restenosis, and corresponding reduced risk of 12-month target lesion revascularization, researchers report (pp. 1264–70). Compared with dual antiplatelet therapy (aspirin plus clopidogrel, addition of cilostazol had these effects: “The in-stent (0.56 ± 0.55 mm vs. 0.68 ± 0.59 mm, p = 0.045) and in-segment (0.32 ± 0.54 mm vs. 0.47 ± 0.54 mm, p = 0.006) late loss were significantly lower in the triple versus dual group, as were 8-month in-stent restenosis (10.8% vs. 19.1%, p = 0.016), in-segment restenosis (12.2% vs. 20.0%, p = 0.028), and 12-month ischemic-driven target lesion revascularization (5.2% vs. 10.0%, p = 0.042) rates. At 12 months, major adverse cardiac events including death, myocardial infarction, and ischemic-driven target lesion revascularization tended to be lower in the triple group than the dual group (7.2% vs. 12.0%, p = 0.07). Percent intimal hyperplasia volume by volumetric intravascular ultrasound analysis was reduced from 27.1 ± 13.2% for the dual group to 22.1 ± 9.9% for the triple group (p = 0.017).” (S-W Park, swpark@amc.seoul.kr)
Mediterranean Diet & Metabolic Syndrome: A meta-analysis of 50 trials that included more than half a million patients demonstrates the significant impact of the Mediterranean diet on cardiovascular disease risk and metabolic syndrome (MS) in adults (pp. 1299–313). “These results are of considerable public health importance, because this dietary pattern can be easily adopted by all population groups and various cultures and cost-effectively serve for primary and secondary prevention of the MS and its individual components,” the authors conclude, adding: “The combined effect of prospective studies and clinical trials showed that adherence to the Mediterranean diet was associated with reduced risk of MS (log hazard ratio: –0.69, 95% confidence interval [CI]: –1.24 to –1.16). Additionally, results from clinical studies (mean difference, 95% CI) revealed the protective role of the Mediterranean diet on components of MS, like waist circumference (–0.42 cm, 95% CI: –0.82 to –0.02), high-density lipoprotein cholesterol (1.17 mg/dl, 95% CI: 0.38 to 1.96), triglycerides (–6.14 mg/dl, 95% CI: –10.35 to –1.93), systolic (–2.35 mm Hg, 95% CI: –3.51 to –1.18) and diastolic blood pressure (–1.58 mm Hg, 95% CI: –2.02 to –1.13), and glucose (–3.89 mg/dl, 95% CI:–5.84 to –1.95), whereas results from epidemiological studies also confirmed those of clinical trials.” (D. B. Panagiotakos, d.b.panagiotakos@usa.net)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 9, 2011 * Vol. 18, No. 46
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Mar. 9 issue of JAMA (2011; 305).
Conflict-of-Interest Reporting in Meta-analyses: In meta-analysis of pharmacologic agents published in high-impact medical journals, information about primary study funding and author-reported conflicts of interest (COIs) was “rarely reported,” a study shows (pp. 1008–17). Investigators selected the three most recently published meta-analyses of randomized controlled trials (RCTs) of patented pharmacologic treatments published in the first 10 months of 2009 in general medicine journals with impact factors of 10 or more, in high-impact journals in five specialty areas with high 2008 sales, and in the Cochrane Database, with these results: “Of 29 meta-analyses reviewed, which included 509 RCTs, only 2 meta-analyses (7%) reported RCT funding sources; and 0 reported RCT author–industry ties or employment by the pharmaceutical industry. Of 318 meta-analyzed RCTs that reported funding sources, 219 (69%) were industry funded; and 91 of 132 (69%) that reported author financial disclosures had 1 or more authors with pharmaceutical industry financial ties. In 7 of the 29 meta-analyses reviewed, 100% of included RCTs had at least 1 form of disclosed COI (pharmaceutical industry funding, author-industry financial ties, or employment), yet only 1 of these 7 meta-analyses reported RCT funding sources, and 0 reported RCT author-industry ties or employment.” (B. D. Thombs, brett.thombs@mcgill.ca)
Long-term Survival of Adult Trauma Patients: In Washington State, in-hospital deaths of adults admitted for trauma declined over the 1995–2008 time period, but 3-year mortality was higher than expected, 16% versus 5.9%, and long-term cumulative mortaility increased, researchers report (pp. 1001–7). A retrospective cohort analysis of the Washington State Trauma Registry shows the following: “Of the 124,421 trauma patients, 7,243 died before hospital discharge and 21,045 died following hospital discharge. Cumulative mortality at 3 years postinjury was 16% (95% confidence interval [CI], 15.8%–16.2%) compared with the expected population cumulative mortality of 5.9% (95% CI, 5.9%–5.9%). In-hospital mortality improved during the 14-year study period from 8% (n = 362) to 4.9% (n = 600), whereas long-term cumulative mortality increased from 4.7% (95% CI, 4.1%–5.4%) to 7.4% (95% CI, 6.8%–8.1%). After adjustments for confounders, patients who were older and those who were discharged to a skilled nursing facility had the highest risk of death. The adjusted hazard ratios (HRs) for death after discharge to a skilled nursing facility compared with that after discharge home were 1.41 (95% CI, 0.72–2.76) for patients aged 18 to 30 years, 1.92 (95% CI, 1.36–2.73) for patients aged 31 to 45 years, 2.02 (95% CI, 1.39–2.93) for patients aged 46 to 55 years, 1.93 (95% CI, 1.40–2.64) for patients aged 56 to 65 years, 1.49 (95% CI, 1.14–1.94) for patients aged 66 to 75 years, 1.54 (95% CI, 1.27–1.87) for patients aged 76 to 80 years, and 1.38 (95% CI, 1.09–1.74) for patients older than 80 years. Other significant predictors of mortality after discharge included maximum head injury score on Abbreviated Injury Score scale (HR, 1.20; 95% CI, 1.13–1.26), Injury Severity Score (HR, 0.98; 95% CI, 0.97–0.98), Functional Independence Measure (HR, 0.89; 95% CI, 0.88–0.91), mechanism of injury being a fall (HR, 1.43; 95% CI, 1.30–1.58), and having Medicare (HR, 1.28; 95% CI, 1.15–1.43) or other government insurance (HR, 1.65; 95% CI, 1.47–1.85).” (S. Arbabi, sarbabi@uw.edu)

>>>PNN NewsWatch
* Lopinavir/ritonavir (Kaletra, Abbott) oral solution should not be used within the first 2 weeks after birth, FDA warned yesterday. In addition, the product should not be given to premature neonates until 14 days after their due date (42 weeks after the first day of the mother’s last menstrual period), the agency said. The oral solution contains alcohol and propylene glycol, and premature babies may be at increased risk for health problems because of their decreased ability to eliminate propylene glycol. FDA said this may explain adverse events—including serious heart, kidney, or breathing problems—observed in premature neonates who have received Kaletra oral solution.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 10, 2011 * Vol. 18, No. 47
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Mar. 10 issue of the New England Journal of Medicine (2011; 364).
Olmesartan & Microalbuminuria in Diabetes: In 4,447 patients with type 2 diabetes, olmesartan delayed the onset of microalbuminuria, researchers report (pp. 907–17). Benefits were not related to blood pressure reduction, as levels were controlled in both treatment and placebo groups. Olmesartan was dosed at 40 mg once daily for a median of 3.2 years, and other antihypertensive agents were reduced to reduce blood pressure to less than 130/80 mm Hg. Results showed: “The target blood pressure (<130/80 mm Hg) was achieved in nearly 80% of the patients taking olmesartan and 71% taking placebo; blood pressure measured in the clinic was lower by 3.1/1.9 mm Hg in the olmesartan group than in the placebo group. Microalbuminuria developed in 8.2% of the patients in the olmesartan group (178 of 2,160 patients who could be evaluated) and 9.8% in the placebo group (210 of 2,139); the time to the onset of microalbuminuria was increased by 23% with olmesartan (hazard ratio for onset of microalbuminuria, 0.77; 95% confidence interval, 0.63 to 0.94; P = 0.01). The serum creatinine level doubled in 1% of the patients in each group. Slightly fewer patients in the olmesartan group than in the placebo group had nonfatal cardiovascular events—81 of 2,232 patients (3.6%) as compared with 91 of 2,215 patients (4.1%) (P = 0.37)—but a greater number had fatal cardiovascular events—15 patients (0.7%) as compared with 3 patients (0.1%) (P = 0.01), a difference that was attributable in part to a higher rate of death from cardiovascular causes in the olmesartan group than in the placebo group among patients with preexisting coronary heart disease (11 of 564 patients [2.0%] vs. 1 of 540 [0.2%], P = 0.02).” (H. Haller, haller.hermann@mh-hannover.de)
Irbesartan in Atrial Fibrillation: Irbesartan 300 mg once daily failed to affect outcomes in patients with atrial fibrillation (pp. 928–38): “9,016 patients were enrolled and followed for a mean of 4.1 years. The mean reduction in systolic blood pressure was 2.9 mm Hg greater in the irbesartan group than in the placebo group, and the mean reduction in diastolic blood pressure was 1.9 mm Hg greater. The first coprimary outcome occurred at a rate of 5.4% per 100 person–years in both groups (hazard ratio with irbesartan, 0.99; 95% confidence interval [CI], 0.91 to 1.08; P = 0.85). The second coprimary outcome occurred at a rate of 7.3% per 100 person–years among patients receiving irbesartan and 7.7% per 100 person–years among patients receiving placebo (hazard ratio, 0.94; 95% CI, 0.87 to 1.02; P = 0.12). The rates of first hospitalization for heart failure (a prespecified secondary outcome) were 2.7% per 100 person–years among patients receiving irbesartan and 3.2% per 100 person–years among patients receiving placebo (hazard ratio, 0.86; 95% CI, 0.76 to 0.98). Among patients who were in sinus rhythm at baseline, there was no benefit of irbesartan in preventing hospitalization for atrial fibrillation or atrial fibrillation recorded on 12-lead electrocardiography, nor was there a benefit in a subgroup that underwent transtelephonic monitoring. More patients in the irbesartan group than in the placebo group had symptomatic hypotension (127 vs. 64) and renal dysfunction (43 vs. 24).” (S. Yusuf, yusufs@mcmaster.ca)

>>>PNN NewsWatch
* The first agent newly marketed for systemic lupus erythematosus in 56 years, belimumab (Benlysta, Human Genome Sciences) was approved yesterday by FDA to treat patients with active, autoantibody-positive lupus who are receiving standard therapy, including corticosteroids, antimalarials, immunosuppressives, and NSAIDs. The drug, administered by intravenous infusion, is the first inhibitor designed to target B-lymphocyte stimulator protein, which may reduce the number of abnormal B cells thought to be a problem in lupus. Two studies of 1,684 patients with lupus demonstrated safety and effectiveness of belimumab. The studies excluded patients who had received prior B-cell targeted therapy or intravenous cyclophosphamide, and those who had active lupus involving the kidneys or CNS. Deaths and serious infections were more common among those taking belimumab, and common adverse effects included nausea, diarrhea, and fever. Pretreatment with antihistamines should be considered to reduce infusion reactions with belimumab.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 11, 2011 * Vol. 18, No. 48
Providing news and information about medications and their proper use

>>>JAPhA Highlights
Source:
Mar/Apr issue of the Journal of the American Pharmacists Association, a theme issue on patient-centered medical homes (2011; 51).
Clinical Pharmacy Services in a Medical Home: At a Washington State primary care clinic, pharmacists’ clinical roles have expanded greatly over the decades since 1981, authors of a descriptive article report (pp. 156–60). In the patient-centered medical home (PCMH), collaborative practice agreements and clinical pharmacy services showed these growth patterns despite the limitations of a fee-for-service environment: “Clinical pharmacy services expanded under the PCMH model. Pharmacist activities included value-added refill authorization services, coordinated patient visits with the PCMH pharmacist and physicians, medication therapy management, diabetes and anticoagulation services, hospital discharge medication reconciliation, and participation in the shared medical appointment.” (S. Erickson, steven.erickson@providence.org)
Pharmacist Integration into a Medical Home: At North Carolina’s Mountain Area Health Education Family Health Center in 2001–11, pharmacists have carved out a unique niche in a PCMH (pp. 161–6): “The Department of Pharmacotherapy is embedded in the family medicine clinic. Three pharmacists and two pharmacy residents are involved in providing direct patient care services, ensuring access to community resources, assisting patients with transitions of care, providing interprofessional education, and participating in continuous quality improvement initiatives. The pharmacists serve as clinical pharmacist practitioners and provide medication therapy management services in a pharmacotherapy clinic, anticoagulation clinics, and an osteoporosis clinic and via an inpatient family medicine service. Multiple learners such as student pharmacists, pharmacy residents, and family medicine residents rotate through the various pharmacy clinics to learn about pharmacotherapeutic principles and the role of the pharmacist in PCMH.” (M. A. Scott, mollie.scott@mahec.net)
Pharmacists Helping Preserve Safety Net: Collaborative medication therapy management (CMTM) was successfully integrated into a safety-net PCMH, researchers report (pp. 167–72). CMTM that included medication assessment, care plan development, and follow-up showed these benefits: “Since October 2008, 695 patients have had a CMTM encounter. An analysis of 209 patients in the mental health clinic indicated that 425 medication-related problems were identified (2.0/patient). Pharmacists made 452 recommendations to resolve problems, and 384 (85%) pharmacist recommendations were accepted by providers and/or patients. For 40 patients in the medical clinic, 205 medication-related problems were identified (5.1/patient). Pharmacists made 217 recommendations to resolve the problems, and 194 (89%) recommendations were accepted.” (L. R. Moczygemba, lrmoczygemba@vcu.edu)
Pharmacist Integration into Medical Home: In a qualitative study of pharmacist services at four Pittsburgh-area family medicine offices that function as medical homes, participants reported improved quality of care, empowered patients, and better workflow (pp. 173–83): “A total of 84 interviews were conducted: 21 interviews with family medicine physicians, 26 with patient care staff, 9 with nonclinical staff, 13 with patients, 6 with pharmacists, and 8 with office managers. Five main themes emerged from each group regarding the integration of a pharmacist, including positive overall feeling; clinical, educational, and time-saving benefits to the various groups; challenges understanding the role of the pharmacist; improved workflow and integration resulting from pharmacist flexibility and motivation; and suggestions to increase the pharmacists’ time in each office. Pharmacists felt that they were accepted within 6 months of the integration process and that time management was a challenge.” (M. S. McGivney, somma@pitt.edu)

>>>PNN NewsWatch
* McNeil-PPC has agreed to not manufacture or distribute drugs from its Fort Washington, PA, facility until FDA certifies compliance with law. Provisions of a consent decree announced yesterday apply to the company and two officers. This and two other affected McNeil plants have been involved in a series of extensive medication product recalls over the past 2 years.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 14, 2011 * Vol. 18, No. 49
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Mar. 12 issue of Lancet (2011; 377).
Quadruple Therapy for H. pylori Eradication: In an open-label, noninferiority trial, omeprazole plus a single capsule with bismuth subcitrate potassium, metronidazole, and tetracycline provided superior eradication of Helicobacter pylori than did standard triple therapy, researchers report (pp. 905–13). The Phase III trial, designed for noninferiority but powered to demonstrate superiority, compared quadruple therapy with standard doses of omeprazole, amoxicillin, and clarithromycin, with these results: “In the per-protocol population (n = 339), the lower bound of the CI for treatment with quadruple therapy was greater than the pre-established non-inferiority margin of −10% (95% CI 15.1–32.3; p < 0.0001). In the intention-to-treat population (n = 440), eradication rates were 80% (174 of 218 participants) in the quadruple therapy group versus 55% (123 of 222) in the standard therapy group (p < 0.0001). Safety profiles for both treatments were similar; main adverse events were gastrointestinal and CNS disorders.” (P. Malfertheiner, peter.malfertheiner@med.ovgu.de)
Eribulin Monotherapy in Metastatic Breast Cancer: Compared with therapy of physician’s choice (TPC), eribulin monotherapy significantly improved overall survival in a Phase III trial of women with locally recurrent or metastatic breast cancer (pp. 914–23). In the open-label EMBRACE trial, this nontaxane microtubule dynamics inhibitor or TPC was provided to patients who had previously received two to five chemotherapy regimens. Results showed: “762 women were randomly allocated to treatment groups (508 eribulin, 254 TPC). Overall survival was significantly improved in women assigned to eribulin (median 13.1 months, 95% CI 11.8–14.3) compared with TPC (10.6 months, 9.3–12.5; hazard ratio 0.81, 95% CI 0.66–0.99; p = 0.041). The most common adverse events in both groups were asthenia or fatigue (270 [54%] of 503 patients on eribulin and 98 [40%] of 247 patients on TPC at all grades) and neutropenia (260 [52%] patients receiving eribulin and 73 [30%] of those on TPC at all grades). Peripheral neuropathy was the most common adverse event leading to discontinuation from eribulin, occurring in 24 (5%) of 503 patients.” (C. Twelves, c.j.twelves@leeds.ac.uk)
Insulin Degludec in Type 2 Diabetes: A new ultra-long-acting basal insulin, insulin degludec, provided equivalent glycemic control to that of insulin glargine in an open-label, Phase II trial (pp. 924–31). Adults with type 2 diabetes and glycosylated hemoglobin levels of 7–11% had these respective responses to two doses of insulin degludec given once daily, a regimen administered three times weekly, and insulin glargine once daily: “At study end, mean HbA1C levels were much the same across treatment groups, at 7.3% (SD 1.1), 7.4% (1.0), 7.5% (1.1), and 7.2% (0.9), respectively. Estimated mean HbA1C treatment differences from insulin degludec by comparison with insulin glargine were 0.08% (95% CI −0.23 to 0.40) for the three dose per week schedule, 0.17% (−0.15 to 0.48) for [a lower daily dose], and 0.28% (−0.04 to 0.59) for [a higher daily dose]. Few participants had hypoglycaemia and the number of adverse events was much the same across groups.” (B. Zinman, zinman@lunenfeld.ca)

>>>PNN NewsWatch
* Stability problems forced a recall of Embeda, King Pharmaceuticals’ formulation of morphine/naltrexone. It will not be available for “many months,” pharmacist.com reports.

>>>PNN JournalWatch
* Impact of Growth Hormone Therapy on Adult Height of Children with Idiopathic Short Stature: Systematic Review, in BMJ, 2011; 342: c7157. (S. Cianfarani, stefano.cianfarani@uniroma2.it)
* Efficacy of Drug Treatments for Generalised Anxiety Disorder: Systematic Review and Meta-Analysis, in
BMJ, 2011; 342: d1199. (D. Baldwin, .S.Baldwin@soton.ac.uk">D.S.Baldwin@soton.ac.uk)
* Update on Human Immunodeficiency Virus (HIV)-2 Infection, in
Clinical Infectious Diseases, 2011; 52: 780–7. (R. T. Gandhi, rgandhi@partners.org)
* The Spectrum of Engagement in HIV Care and Its Relevance to Test-and-Treat Strategies for Prevention of HIV Infection, in
Clinical Infectious Diseases, 2011; 52: 793–800. (E. M. Gardner, edward.m.gardner@dhha.org)
* The Benefits of Health Information Technology: A Review of the Recent Literature Shows Predominantly Positive Results, in
Health Affairs, 2011; 30: 464–71. (M. B. Buntin, Melinda.buntin@hhs.gov)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 15, 2011 * Vol. 18, No. 50
Providing news and information about medications and their proper use

>>>Internal Medicine Report I
Source:
Early-release articles from the Annals of Internal Medicine (2011; 154).
Blood Pressure Target in CKD: In adults with chronic kidney disease, target blood pressures of 125/75 to 130/80 mm Hg may not produce added benefits, compared with 140/90, a systematic review of 3 trials of 2,272 participants shows (early release): “Lower-quality evidence suggests that a low target may be beneficial in subgroups with proteinuria greater than 300 to 1000 mg/d. Participants in the low target groups needed more antihypertensive medications and had a slightly higher rate of adverse events.” (K. Uhlig, kuhlig@tuftsmedicalcenter.org)
CER of Antidiabetic Medications in Type 2 Diabetes: Metformin is the best first-line agent for treating type 2 diabetes, a comparative effectiveness research study reports (early release). Two-drug combinations were about as effective at lowering glycosylated hemoglobin as metformin but produced more hypoglycemia and other adverse events, the authors report, adding: “Evidence on long-term clinical outcomes (all-cause mortality, cardiovascular disease, nephropathy, and neuropathy) was of low strength or insufficient. Most medications decreased the hemoglobin A1c level by about 1 percentage point and most 2-drug combinations produced similar reductions. Metformin was more efficacious than the [dipeptidyl peptidase-4 (DPP-4)] inhibitors, and compared with thiazolidinediones or sulfonylureas, the mean differences in body weight were about −2.5 kg. Metformin decreased low-density lipoprotein cholesterol levels compared with pioglitazone, sulfonylureas, and DPP-4 inhibitors. Sulfonylureas had a 4-fold higher risk for mild or moderate hypoglycemia than metformin alone and, in combination with metformin, had more than a 5-fold increased risk compared with metformin plus thiazolidinediones. Thiazolidinediones increased risk for congestive heart failure compared with sulfonylureas and increased risk for bone fractures compared with metformin. Diarrhea occurred more often with metformin than with thiazolidinediones.” (W. L. Bennett, wbennet5@jhmi.edu)

>>>Internal Medicine Report II
Source:
Early-release articles from the Archives of Internal Medicine (2011; 171).
Stopping Smoking Before Surgery: Concerns that smoking cessation before surgery worsens clinical outcomes are unfounded, according to results of a systematic review with meta-analysis (doi: 10.1001/archinternmed.2011.97): “Nine studies met the inclusion criteria. One found a beneficial effect of recent quitting compared with continuing smoking, and none identified any detrimental effects. In meta-analyses, quitting smoking within 8 weeks before surgery was not associated with an increase or decrease in overall postoperative complications for all available studies (relative risk [RR], 0.78; 95% confidence interval [CI], 0.57–1.07), for a group of 3 studies with high-quality scores (RR, 0.57; 95% CI, 0.16–2.01), or for a group of 4 studies that specifically evaluated pulmonary complications (RR, 1.18; 95% CI, 0.95–1.46).” (K. Myers, k.myers@qmul.ac.uk)
Bupropion for Smoking Cessation in ACS: Use of bupropion failed to increase abstinence rates among 149 smokers hospitalized with acute coronary syndrome who were receiving continuous, intensive nurse counseling, researchers report (doi: 10.1001/archinternmed.2011.72). Over 8 weeks of treatment with slow-release bupropion or placebo, researchers observed these changes in smoking abstinence and clinical events: “Abstinence rates at 3 months were 45% and 44% in the bupropion SR and placebo groups, respectively (P = .99); 37% vs 42% (P = .61) at 6 months; and 31% vs 33% (P = .86) at 1 year. On multivariate analysis, an invasive procedure performed during index hospitalization was an independent predictor for smoking abstinence at 1 year (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.22–14.19). Presence of adverse effects attributed to treatment was a negative predictor for smoking cessation (OR, 0.23; 95% CI, 0.07–0.78). Treatment with bupropion SR was not associated with an increase in clinical events or change in blood pressure or body mass index, but dizziness was more common compared with placebo (14% vs 1.4%; P = .005).” (D. Planer)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 16, 2011 * Vol. 18, No. 51
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Mar. 16 issue of JAMA (2011; 305).
High-Dose Clopidogrel After PCI: Clinical outcomes were not improved by use of high-dose clopidogrel among patients with elevated on-treatment platelet reactivity after percutaneous coronary interventions, according to results of the Gauging Responsiveness with A VerifyNow assay—Impact on Thrombosis And Safety (GRAVITAS) trial (pp. 1097–105). Study participants had high on-treatment reactivity 12 to 24 hours after PCI with drug-eluting stents. Clopidogrel 600 mg initially followed by 150 mg daily for 6 months showed these effects on a primary end point of 6-month incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis, compared with no loading dose and standard doses of 75 mg daily: “At 6 months, the primary end point had occurred in 25 of 1,109 patients (2.3%) receiving high-dose clopidogrel compared with 25 of 1,105 patients (2.3%) receiving standard-dose clopidogrel (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.58–1.76; P = .97). Severe or moderate bleeding was not increased with the high-dose regimen (15 [1.4%] vs 25 [2.3%], HR, 0.59; 95% CI, 0.31–1.11; P = .10). Compared with standard-dose clopidogrel, high-dose clopidogrel provided a 22% (95% CI, 18%–26%) absolute reduction in the rate of high on-treatment reactivity at 30 days (62%; 95% CI, 59%–65% vs 40%; 95% CI, 37%–43%; P < .001).” (M. J. Price, price.matthew@scrippshealth.org)
“The GRAVITAS investigators have conducted the largest trial of personalized antiplatelet therapy thus far,” write editorialists (
pp. 1136–7). “The valuable information gained from the GRAVITAS trial can inform future trials. Even though GRAVITAS demonstrated that platelet function testing after drug-eluting stent placement does not improve outcomes if high-dose clopidogrel is used as the remedy, it is hoped that future studies evaluating different platelet function cutpoints and more potent P2Y12 inhibitors will be effective.” (P. A. Gurbel, pgurbel@lifebridgehealth.org)
Smoking Prevalence Rates in U.S., California: High-intensity smoking declined markedly in the U.S. between 1965 and 2007, a study shows, and prevalence rates in California declined even more as a result of decreased rates of smoking initiation and probably increased cessation (pp. 1106–12). Data from the National Health Interview Surveys, 1965–1994 and Current Population Survey Tobacco Supplements, 1992–2007 show these smoking patterns for 1.7 million Americans and 139,000 Californians: “In 1965, 23.2% of adults in California (95% confidence interval [CI], 19.6%–26.8%) and 22.9% of adults in the remaining United States (95% CI, 22.1%–23.6%) were high-intensity smokers, representing 56% of all smokers. By 2007, this prevalence was 2.6% (95% CI, 0.0%–5.6%) or 23% of smokers in California and 7.2% (95% CI, 6.4%–8.0%) or 40% of smokers in the remaining United States. Among individuals (US residents excluding California) born between 1920–1929, the prevalence of moderate/high-intensity smoking (≥10 [cigarettes per day]) was 40.5% (95% CI, 38.3%–42.7%) in 1965. Moderate/high-intensity smoking declined across successive birth cohorts, and for the 1970–1979 birth cohort, the highest rate of moderate/high-intensity smoking was 9.7% (95% CI, 7.7%–11.7%) in California and 18.3% (95% CI, 16.4%–20.2%) in the remaining United States. There was a marked decline in moderate/high-intensity smoking at older ages in all cohorts, but this was greater in California. By age 35 years, the prevalence of moderate/high-intensity smoking in the 1970–1979 birth cohort was 4.6% (95% CI, 3.0%–6.1%) in California and 13.5% (95% CI, 11.8%–15.1%) in the remaining United States.” (J. P. Pierce, jppierce@ucsd.edu)
Diagnoses & Fatality Rates: Hospital regions with a greater frequency of diagnoses have lower case-fatality rates for nine chronic conditions such as coronary artery disease and kidney failure, according to a study of 5 million Medicare beneficiaries (pp. 1113–8). In 2007, the mean number of chronic conditions diagnosed among Medicare beneficiaries across 306 hospital referral regions was 0.90. The mean number of chronic conditions diagnosed per Medicare beneficiary ranged from 0.58 in Grand Junction, CO, and Idaho Falls, ID, to 1.23 in Miami and McAllen, TX. As diagnosis rates increased, case-fatality rates fell progressively. (H. G. Welch, h.gilbert.welch@dartmouth.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 17, 2011 * Vol. 18, No. 52
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Mar. 17 issue of the New England Journal of Medicine (2011; 364).
Omalizumab for Asthma in Inner-City Children: The anti-IgE agent omalizumab proved a very effective addition to standard asthma control therapies in a population of inner-city children, nearly eliminating seasonal peaks in exacerbations and reducing the need for other medications to control asthma (pp. 1005–15). Researchers report these results when the drug was added to guidelines-based therapy over a 60-week period: “Among 419 participants who underwent randomization (at which point 73% had moderate or severe disease), omalizumab as compared with placebo significantly reduced the number of days with asthma symptoms, from 1.96 to 1.48 days per 2-week interval, a 24.5% decrease (P < 0.001). Similarly, omalizumab significantly reduced the proportion of participants who had one or more exacerbations from 48.8 to 30.3% (P < 0.001). Improvements occurred with omalizumab despite reductions in the use of inhaled glucocorticoids and long-acting beta-agonists.” (W. W. Busse, wwb@medicine.wisc.edu)
Cytarabine Dose in Acute Myeloid Leukemia: Lower doses of cytarabine can be used for induction therapy in acute myeloid leukemia, according to a study of 860 patients (pp. 1027–36). Comparing intermediate cytarabine doses (200 mg/sq m during cycle 1 of induction therapy and 1000 mg/sq m twice daily during cycle 2 of induction therapy) with high doses (1000 mg/sq m every 12 hours in cycle 1 and 2000 mg/sq m twice daily in cycle 2), the investigators found these results: “At a median follow-up of 5 years, no significant differences were noted between the intermediate-dose group and the high-dose group with respect to complete remission rates (80% and 82%, respectively), probability of relapse, event-free survival at 5 years (34% and 35%), or overall survival (40% and 42%). High-dose cytarabine provided no clear advantage in any prognostic subgroup. The high-dose treatment resulted in higher incidences of grade 3 and grade 4 toxic effects (in cycle 1), prolonged hospitalization, and delayed neutrophil recovery (in cycle 2) and platelet recovery (in cycles 2 and 3).” (B. Löwenberg, b.lowenberg@erasmusmc.nl)
Quality of Life with Drug-Eluting Stents: While differences were small, significantly greater relief of angina was observed when patients received coronary-artery bypass grafting (CABG) rather than percutaneous coronary intervention (PCI) with drug-eluting stents, researchers report (pp. 1016–26). The data are consistent with evidence showing superiority of CABG over PCI with bare-metal stents, the group reports, adding these details on 1,800 patients in the current trial and their quality-of-life scores on the Seattle Angina Questionnaire (SAQ) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36): “The scores on each of the SAQ and SF-36 subscales were significantly higher at 6 and 12 months than at baseline in both groups. The score on the angina-frequency subscale of the SAQ increased to a greater extent with CABG than with PCI at both 6 and 12 months (P = 0.04 and P = 0.03, respectively), but the between-group differences were small (mean treatment effect of 1.7 points at both time points). The proportion of patients who were free from angina was similar in the two groups at 1 month and 6 months and was higher in the CABG group than in the PCI group at 12 months (76.3% vs. 71.6%, P = 0.05). Scores on all the other SAQ and SF-36 subscales were either higher in the PCI group (mainly at 1 month) or were similar in the two groups throughout the follow-up period.” (D. J. Cohen, dcohen@saint-lukes.org)

>>>PNN NewsWatch
* Gadobutrol (Gadavist, Bayer), a gadolinium-based contrast agent, has been approved by FDA for use in patients undergoing magnetic resonance imaging of the central nervous system. It helps to detect and visualize lesions of the blood brain barrier and any abnormal blood supply and circulation in the CNS. Gadobutrol, the sixth gadolinium-based contrast agent (GBCA) approved by FDA for CNS MRIs, is indicated for adults and children ages 2 years and older. It is more concentrated than the other GBCAs and should be administered at half the volume. Two clinical studies involving 657 patients and other trial data established the safety and efficacy of Gadavist. All GBCAs, including gadobutrol, carry boxed warnings of a risk of nephrogenic systemic fibrosis.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 18, 2011 * Vol. 18, No. 53
Providing news and information about medications and their proper use

>>>Infectious Diseases Report
Source:
Mar. 15 issue of Clinical Infectious Diseases (2011; 52).
I.V. Peramivir for Pandemic Influenza: Made available in the U.S. under an emergency investigational new drug regulation issued by FDA, intravenous peramivir was safe and effective in patients hospitalized with infections of 2009 influenza A/H1N1, an analysis shows (pp. 695–706). “From April through October 2009, peramivir was requested for 42 patients and administered to 20 adults and 11 children,” authors write. “At hospitalization, all patients had rapidly progressing, radiographically confirmed viral pneumonia with respiratory failure, and all but 1 patient required mechanical ventilation. In most patients, including 1 person with documented oseltamivir-resistant infection, the illness had progressed despite oseltamivir treatment. Peramivir was administered for 1–14 days (median duration, 10 days). The 14-day, 28-day, and 56-day survival rates were 76.7%, 66.7%, and 59.0%, respectively. Peramivir was generally well tolerated.” (J. Hernandez, jhernandez@biocryst.com)
Pneumococcal Vaccines, Schedules in Adults: Combining two available pneumococcal vaccines in adults provides no greater immunogenicity than a single dose of the 23-valent formulation, researchers report (pp. 736–42). The open-label study tested whether priming doses of the 7-valent pneumococcal conjugate vaccine (PCV7) would enhance the generally short-lived responses to the 23-valent plain polysaccharide vaccine (23vP),with these results: “23vP administered after priming with 2 doses of PCV7 produced significantly higher antibody concentrations for 3 of the 7 PCV7 serotypes, compared with vaccination with a single dose of 23vP; however, the same immunogenicity could be achieved with a single dose of PCV7. Prior vaccination with 23vP attenuated the antibody response to subsequent PCV7, which was not restored by additional doses of PCV7.” (R. Lazarus, rajeka.lazarus@doctors.net.uk)

>>>Geriatrics Highlights
Source:
Mar. issue of the Journal of the American Geriatrics Society (2011; 59).
Hypertension & Falls: Older patients with hypertension and systolic orthostatic hypotension (SOH) are at increased risk of falls within 1 year, a study shows, but hypertension control, even if orthostatic hypotension (OH) is present, is not associated with falls, according to a study of 722 adults aged 70 years or older (pp. 383–9). Blood pressures, SOH, and diastolic OH were measured at baseline, and presence of hypertension and use of control medications recorded. Combining those data with information recorded by patients in calendars, the investigators determined these patterns, with falls defined as at least two episodes during the following year: “OH was highest in participants with uncontrolled hypertension; SOH at 1 minute was 19% in participants with uncontrolled hypertension, 5% in those with controlled hypertension, and 2% in those without hypertension (P ≤ .001). Participants with SOH at 1 minute and uncontrolled hypertension were at greater risk of falls (hazard ratio = 2.5, 95% confidence interval = 1.3–5.0) than those with uncontrolled hypertension without OH. OH by itself was not associated with falls.” (A. Gangavati, agangava@bidmc.harvard.edu)
Opioids & Fractures: Older patients with arthritis who initiate opioid therapy are at greater risk of fractures, compared with NSAID treatment, a retrospective cohort study conducted in two states reports (pp. 430–8). The risk was especially high in the first 2 weeks of treatment with short-acting opioids, the data show: “There were 587 fracture events among the participants initiating opioids (120 fractures per 1,000 person–years) and 38 fracture events among participants initiating NSAIDs (25 fractures per 1,000 person–years) (hazard ratio (HR) = 4.9, 95% confidence interval (CI) =3 .5–6.9). Fracture risk was greater with higher opioid dose. Risk was greater for short-acting opioids (HR = 5.1, 95% CI = 3.7–7.1) than for long-acting opioids (HR = 2.6, 95% CI = 1.5–4.4), even in participants taking equianalgesic doses, with differential fracture risk apparent for the first 2 weeks after starting opioids but not thereafter.” (M. Miller, mmiller@hsph.harvard.edu)

>>>PNN NewsWatch
* FDA and the European Medicines Agency announced a pilot program, Quality by Design, that will permit parallel evaluation of new drug marketing applications submitted to both agencies.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 21, 2011 * Vol. 18, No. 54
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Mar. 19 issue of Lancet (2011; 377).
Treatment for Fecal Incontinence: Patients with fecal incontinence benefitted from injection of a bulking agent into the anal canal, researchers report (pp. 997–1003). In a controlled trial of dextranomer in stabilized hyaluronic acid (NASHA Dx), patients had these outcomes after receiving transanal submucosal drug or sham injections: “278 patients were screened for inclusion, of whom 206 were randomised assigned to receive NASHA Dx (n = 136) or sham treatment (n = 70). 71 patients who received NASHA Dx (52%) had a 50% or more reduction in the number of incontinence episode, compared with 22 patients who received sham treatment (31%; odds ratio 2.36, 95% CI 1.24–4.47, p = 0.0089). We recorded 128 treatment-related adverse events, of which two were serious (1 rectal abscess and 1 prostatic abscess).” (W. Graf, wilhelm.graf@akademiska.se)

>>>BMJ Highlights
Source:
Early-release articles from BMJ (2011; 342).
Cardiovascular Effects of Thiazolidinediones: Rosiglitazone is associated with higher risks of congestive heart failure, myocardial infarction, and death, compared with pioglitazone, according to a systematic review and meta-analysis of observational studies (d1309): “Cardiovascular outcomes from 16 observational studies (4 case–control studies and 12 retrospective cohort studies), including 810,000 thiazolidinedione users, were evaluated after a detailed review of 189 citations. Compared with pioglitazone, use of rosiglitazone was associated with a statistically significant increase in the odds of myocardial infarction (n = 15 studies; odds ratio 1.16, 95% confidence interval 1.07 to 1.24; P < 0.001; I2 = 46%), congestive heart failure (n = 8; 1.22, 1.14 to 1.31; P < 0.001; I2 = 37%), and death (n = 8; 1.14, 1.09 to 1.20; P < 0.001; I2 = 0%). Numbers needed to treat to harm (NNH), depending on the population at risk, suggest 170 excess myocardial infarctions, 649 excess cases of heart failure, and 431 excess deaths for every 100,000 patients who receive rosiglitazone rather than pioglitazone.” (Y. K. Loke, y.loke@uea.ac.uk)
Glutamine, Selenium in Parenteral Nutrition: Intention-to-treat analysis in a controlled factorial trial showed no overall benefits of glutamine or selenium supplementation of parenteral nutrition fluids administered to critically ill patients (d1542). One subgroup among the 502 patients had fewer new infections, the authors report: “Selenium supplementation did not significantly affect patients developing a new infection (126/251 v 139/251, odds ratio 0.81 (95% CI 0.57 to 1.15)), except for those who had received ≥5 days of supplementation (odds ratio 0.53 (0.30 to 0.93)). There was no overall effect of glutamine on new infections (134/250 v 131/252, odds ratio 1.07 (0.75 to 1.53)), even if patients received ≥5 days of supplementation (odds ratio 0.99 (0.56 to 1.75)). Six month mortality was not significantly different for selenium (107/251 v 114/251, odds ratio 0.89 (0.62 to 1.29)) or glutamine (115/250 v 106/252, 1.18 (0.82 to 1.70)). Length of stay, days of antibiotic use, and modified [Sepsis-related Organ Failure Assessment] score were not significantly affected by selenium or glutamine supplementation.” (P. J. D. Andrews, p.andrews@ed.ac.uk)

>>>PNN JournalWatch
* Aerosol Drug Delivery: Developments in Device Design and Clinical Use, in Lancet, 2011; 377: 1032–45. (M. B. Dolovich, mdolovic@mcmaster.ca)
* Effect of Statins on Atrial Fibrillation: Collaborative Meta-analysis of Published and Unpublished Evidence from Randomised Controlled Trials, in
BMJ, 2011; 342: d1250. (K. Rahimi, kazem.rahimi@cardiov.ox.ac.uk)
* Prevention of Pain on Injection of Propofol: Systematic Review and Meta-Analysis, in
BMJ, 2011; 342: d1110. (C. C. Apfel, apfelc@anesthesia.ucsf.edu)
* Future Therapies for Food Allergies, in
Journal of Allergy and Clinical Immunology, 2011; 127: 558–73. (H. A. Sampson, hugh.sampson@mssm.edu)
* Surrogate Markers of Cardiovascular Disease in CKD: What’s Under the Hood?, in
American Journal of Kidney Diseases, 2011; 57: 488–97. (M. F. Rubin, mfrubin@partners.org)
* Management of Gram-Positive Coccal Bacteremia and Hemodialysis, in
American Journal of Kidney Diseases, 2011; 57: 624–40. (G. N. Forrest, forrestg@ohsu.edu)
* Pharmacy Waste, Fraud, and Abuse in Health Care Reform, in
Journal of the American Pharmacists Association, 2011; 51: e3–e16. (L. A. Carpenter, carpenter@lcarpenterlawfirm.com)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 22, 2011 * Vol. 18, No. 55
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Early-release article from the New England Journal of Medicine (2011; 364).
Dalteparin v. Heparin in Critically Ill Patients: In a multicenter trial of 3,764 patients in intensive care, dalteparin was not superior to unfractionated heparin for prevention of deep-vein thrombosis, researchers report (doi: 10.1056/NEJMoa1014475). In the study, released early in conjunction with presentation at the International Symposium on Intensive Care and Emergency Medicine, patients received either subcutaneous dalteparin 5000 IU once daily or unfractionated heparin 5000 IU twice daily, with these results: “There was no significant between-group difference in the rate of proximal leg deep-vein thrombosis, which occurred in 96 of 1,873 patients (5.1%) receiving dalteparin versus 109 of 1,873 patients (5.8%) receiving unfractionated heparin (hazard ratio in the dalteparin group, 0.92; 95% confidence interval [CI], 0.68 to 1.23; P = 0.57). The proportion of patients with pulmonary emboli was significantly lower with dalteparin (24 patients, 1.3%) than with unfractionated heparin (43 patients, 2.3%) (hazard ratio, 0.51; 95% CI, 0.30 to 0.88; P = 0.01). There was no significant between-group difference in the rates of major bleeding (hazard ratio, 1.00; 95% CI, 0.75 to 1.34; P = 0.98) or death in the hospital (hazard ratio, 0.92; 95% CI, 0.80 to 1.05; P = 0.21). In prespecified per-protocol analyses, the results were similar to those of the main analyses, but fewer patients receiving dalteparin had heparin-induced thrombocytopenia (hazard ratio, 0.27; 95% CI, 0.08 to 0.98; P = 0.046).” (D. Cook, debcook@mcmaster.ca)

>>>Oncology Highlights
Source:
Mar. 20 issue of the Journal of Clinical Oncology (2011; 29).
Denosumab v. Zoledronic Acid in Treating Bone Metastases: Among 1,776 patients with advanced cancer and bone metastases or myeloma, denosumab was noninferior and trending to superiority to zoledronic acid (ZA), a study shows (pp. 1125–32). The agent, a fully human monoclonal anti-receptor activator of nuclear factor kappa-B ligand antibody, had these effects on first on-study skeletal-related events (SRE) when used in monthly doses of 120 mg and compared with monthly intravenous ZA 4 mg: “Denosumab was noninferior to ZA in delaying time to first on-study SRE (hazard ratio, 0.84; 95% CI, 0.71 to 0.98; P = .0007). Although directionally favorable, denosumab was not statistically superior to ZA in delaying time to first on-study SRE (P = .03 unadjusted; P = .06 adjusted for multiplicity) or time to first-and-subsequent (multiple) SRE (rate ratio, 0.90; 95% CI, 0.77 to 1.04; P = .14). Overall survival and disease progression were similar between groups. Hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred at similarly low rates in both groups. Acute-phase reactions after the first dose occurred more frequently with ZA, as did renal adverse events and elevations in serum creatinine based on National Cancer Institute Common Toxicity Criteria for Adverse Events grading.” (D. Henry, davidhenry@pennoncology.com)

>>>Neurology Report
Source:
Mar. issue of Neurology (2011; 76).
Stem Cell Transplantation for MS: Hemopoietic stem cell transplantation (HSCT) is not an intervention that should be used in the treatment of all patients with multiple sclerosis (MS), according to a Phase I/II study of 35 patients (pp. 1066–70). The technique may be useful, though, in management of disease in patients with more aggressive cases: “Disease progression-free survival (PFS) at 15 years is 44% for patients with active CNS disease and 10% for those without (p = 0.01); median time to progression was 11 (95% confidence interval 0–22) and 2 (0–6) years. Improvements by 0.5–5.5 (median 1) Expanded Disability Status Scale (EDSS) points were observed in 16 cases lasting for a median of 2 years. In 9 of these patients, EDSS scores did not progress above baseline scores. Two patients died, at 2 months and 2.5 years, from transplant-related complications. Gadolinium-enhancing lesions were significantly reduced after mobilization but were maximally and persistently diminished post-HSCT.” (V. K. Kimiskidis, kimiskid@med.auth.gr)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 23, 2011 * Vol. 18, No. 56
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Mar. 23 issue of JAMA (2011; 305).
Hydrocortisone in Multiple Trauma: Stress doses of hydrocortisone decrease the risk of hospital-acquired pneumonia in patients who have been intubated following multiple trauma, researchers report (pp. 1201–9). In the HYPOLYTE (Hydrocortisone Polytraumatise) study, patients received either placebo or intravenous hydrocortisone 200 mg/d for 5 days, followed by 100 mg on day 6 and 50 mg on day 7, with these results: “An intention-to-treat (ITT) analysis included the 149 patients, a modified ITT analysis included 113 patients with corticosteroid insufficiency. In the ITT analysis, 26 of 73 patients (35.6%) treated with hydrocortisone and 39 of 76 patients (51.3%) receiving placebo developed hospital-acquired pneumonia by day 28 (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.30–0.83; P = .007). In the modified ITT analysis, 20 of 56 patients (35.7%) in the hydrocortisone group and 31 of 57 patients (54.4%) in the placebo group developed hospital-acquired pneumonia by day 28 (HR, 0.47; 95% CI, 0.25–0.86; P = .01). Mechanical ventilation–free days increased with hydrocortisone by 4 days (95% CI, 2-7; P = .001) in the ITT analysis and 6 days (95% CI, 2–11; P < .001) in the modified ITT analysis. Hyponatremia was observed in 7 of 76 (9.2%) in the placebo group vs none in the hydrocortisone group (absolute difference, −9%; 95% CI, −16% to −3%; P = .01). Four of 76 patients (5.3%) in the placebo group and 6 of 73 (8.2%) in the hydrocortisone group died (absolute difference, 3%; 95% CI, −5% to 11%; P = .44).” (K. Asehnoune, karim.asehnoune@chu-nantes.fr)
Writing of the “many unanswered questions” surrounding the use of steroids after severe injury, editorialists point out (
pp. 1242–3): “The well-designed HYPOLYTE study suggests a potential benefit of early steroid administration for severely injured patients with corticosteroid insufficiency, but before changing clinical practice, a larger study is needed to define the effects of steroid use on mortality. In addition, a better understanding of the true incidence of corticosteroid insufficiency and the mechanism of manipulation of the immune-inflammatory response after injury would better guide this therapeutic approach.” (E. M. Bulger, ebulger@u.washington.edu)
Fibrate Use in U.S. & Canada: In the U.S. over the past decade, prescriptions for fibrates and fenofibrate in particular have risen, but use of these agents in Canada has remained level, a study shows (pp. 1217–24). Investigators analyzed population-level, observational cohort data from IMS Health between 2002 and 2009 to make these observations: “In the United States, fibrate prescriptions dispensed increased from 336 prescriptions/100,000 population in January 2002 to 730 prescriptions/100,000 population in December 2009, an increase of 117.1% (95% confidence interval [CI], 116.0%–117.9%), whereas in Canada, fibrate prescriptions increased from 402 prescriptions/100,000 population in January 2002 to 474 prescriptions/100,000 population in December 2009, an increase of 18.1% (95% CI, 17.9%–18.3%) (P <.001). In the United States, fenofibrate prescriptions dispensed increased from 150 prescriptions/100,000 population in January 2002 to 440 prescriptions/100,000 population in December 2009, an increase of 159.3% (95% CI, 157.7%–161.0%), comprising 47.9% of total fibrate prescriptions in 2002 and 65.2% in 2009. In Canada, fenofibrate prescriptions increased from 321 prescriptions/100,000 population in January 2002 to 429 prescriptions/100,000 population in December 2009. The annual ratio of generic to brand-name fenofibrate use in the United States ranged from 0:1 to 0.09:1 between 2002 and 2008, while the ratio in Canada steadily increased from 0.51:1 to 1.89:1 between 2005 and 2008. In the United States, crude fenofibrate expenditures increased from $11,535/100,000 population/month in 2002 to $44,975/100,000 population/month in 2009, while the rates in Canada declined from $17,695/100,000 population/month in 2002 to $16,112/100,000 population/month in 2009. Fibrate expenditures per 100,000 population were 3-fold higher in 2009 in the United States compared with Canada.” (C. A. Jackevicius, cjackevicius@westernu.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 24, 2011 * Vol. 18, No. 57
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Mar. 24 issue of the New England Journal of Medicine (2011; 364).
Tiotropium in COPD: In patients with moderate to very severe chronic obstructive pulmonary disease, tiotropium was more effective than salmeterol for prevention of exacerbations, a study shows (pp. 1093–103). The 1-year trial compared 18-mcg once-daily doses of the anticholinergic agent against the beta-2 agonist salmeterol 50 mcg, with these results: “A total of 7,376 patients were randomly assigned to and treated with tiotropium (3,707 patients) or salmeterol (3,669 patients). Tiotropium, as compared with salmeterol, increased the time to the first exacerbation (187 days vs. 145 days), with a 17% reduction in risk (hazard ratio, 0.83; 95% confidence interval [CI], 0.77 to 0.90; P < 0.001). Tiotropium also increased the time to the first severe exacerbation (hazard ratio, 0.72; 95% CI, 0.61 to 0.85; P < 0.001), reduced the annual number of moderate or severe exacerbations (0.64 vs. 0.72; rate ratio, 0.89; 95% CI, 0.83 to 0.96; P = 0.002), and reduced the annual number of severe exacerbations (0.09 vs. 0.13; rate ratio, 0.73; 95% CI, 0.66 to 0.82; P < 0.001). Overall, the incidence of serious adverse events and of adverse events leading to the discontinuation of treatment was similar in the two study groups. There were 64 deaths (1.7%) in the tiotropium group and 78 (2.1%) in the salmeterol group.” (L. M. Fabbri, leonardo.fabbri@unimore.it)
These results need to be replicated as new beta-2 agonists emerge, writes an editorialist (
pp. 1167–8): “The main implications of this trial are for the initial care of symptomatic patients with moderate disease and a history of recent exacerbations. The trial evidence suggests that with respect to exacerbation outcomes, tiotropium, administered once daily, is superior to salmeterol, administered twice daily. However, novel, once-daily, long-acting beta-2 agonists such as indacaterol are now becoming available in Europe, and there is some evidence that outcomes with indacaterol are similar to those with tiotropium. There is no evidence for the superiority of tiotropium in patients with mild COPD (those in whom the FEV1 is >70% of the predicted value) or symptomatic patients with moderate COPD but without a history of exacerbations. However, in patients with progressive COPD, combinations of inhaled long-acting beta-2 agonists, long-acting anticholinergic agents, glucocorticoids, and new antiinflammatory agents such as oral phosphodiesterase-4 inhibitors may be indicated. Future trials involving patients with COPD will need to study which therapies and which specific combinations are optimal for which COPD phenotypes and disease severities, so that we can reduce the adverse effects of this disabling disease.” (J. A. Wedzicha)
Pioglitazone for Diabetes Prevention: Fewer patients with impaired glucose tolerance developed diabetes when taking pioglitazone, compared with placebo, but at the cost of significant weight gain and edema, researchers report (pp. 1104–15). Over a median of 2.4 years, these patterns were noted among 602 adults: “Annual incidence rates for type 2 diabetes mellitus were 2.1% in the pioglitazone group and 7.6% in the placebo group, and the hazard ratio for conversion to diabetes in the pioglitazone group was 0.28 (95% confidence interval, 0.16 to 0.49; P < 0.001). Conversion to normal glucose tolerance occurred in 48% of the patients in the pioglitazone group and 28% of those in the placebo group (P < 0.001). Treatment with pioglitazone as compared with placebo was associated with significantly reduced levels of fasting glucose (a decrease of 11.7 mg per deciliter vs. 8.1 mg per deciliter [0.7 mmol per liter vs. 0.5 mmol per liter], P < 0.001), 2-hour glucose (a decrease of 30.5 mg per deciliter vs. 15.6 mg per deciliter [1.6 mmol per liter vs. 0.9 mmol per liter], P < 0.001), and HbA1c (a decrease of 0.04 percentage points vs. an increase of 0.20 percentage points, P < 0.001). Pioglitazone therapy was also associated with a decrease in diastolic blood pressure (by 2.0 mm Hg vs. 0.0 mm Hg, P = 0.03), a reduced rate of carotid intima–media thickening (31.5%, P = 0.047), and a greater increase in the level of high-density lipoprotein cholesterol (by 7.35 mg per deciliter vs. 4.5 mg per deciliter [0.4 mmol per liter vs. 0.3 mmol per liter], P = 0.008). Weight gain was greater with pioglitazone than with placebo (3.9 kg vs. 0.77 kg, P < 0.001), and edema was more frequent (12.9% vs. 6.4%, P = 0.007).” (R. A. DeFronzo, albarado@uthscsa.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 25, 2011 * Vol. 18, No. 58
Providing news and information about medications and their proper use

>>>Rheumatology Report
Source:
Mar. issue of Arthritis & Rheumatism (2011; 63).
Reduced-Dose Rituximab in RA: The degree of B-cell depletion provides a marker of rituximab efficacy, and patients with low baseline counts may be candidates for lower doses of the agent, a study shows (pp. 603–8). Investigators administered two 500-mg infusions of rituximab to 19 patients, while 61 patients were treated with two 1,000-mg rituximab infusions, with these results: “The median B cell count was numerically higher at all time points following therapy in the 500 mg rituximab group. Twenty-five percent of patients in the 500 mg rituximab group had complete depletion at 2 weeks, compared with 49% of those in the 1,000 mg rituximab group. Complete depletion at 2 weeks after treatment with 500 mg rituximab was associated with lower baseline preplasma cell counts (P = 0.047). Most patients responded after either dose, but response was related to B cell depletion. Notably, in the 500 mg rituximab group all patients with complete depletion had a [European League Against Rheumatism] good response (P = 0.011).” (D. McGonagle, d.g.mcgonagle@leeds.ac.uk)
An editorialist critiques this small study and provides this input on the next steps in research (
pp. 594–6): “These data are important for our understanding of the relationships between B cell depletion and clinical efficacy, and they clearly shed new light on the discussion of rituximab dosages…. In this respect, it is important to emphasize that the study by Vital et al was not a randomized study; while 2 different rituximab dosages were used, these were chosen by the treating physician based on considerations that may very well have influenced the results. In particular, the 1,000 mg group included more patients in whom anti-TNF agents had previously been used without success, and this patient profile has in some studies been associated with lesser responses. Nevertheless, the fact that 63% of patients responded to the lower dose remains interesting. Vital et al’s discussion of this topic is extremely scholarly and a pleasure to read. I do find myself disagreeing with their suggestion that ‘an appropriately powered randomized trial’ is now needed to compare the 2 rituximab doses—in my view, such trials have already been done, and they showed either no or very modest differences between the doses, and besides, a trial with data at the group level is probably not the way to go. I would much rather put my money on systematic studies in individual patients of the same type that Vital et al have presented for us, and which I am sure they will continue to perform.” (R. F. van Vollenhoven, ronald.van.vollenhoven@ki.se)
Rituximab with TNF Inhibitor/MTX in RA: Rituximab was safe when used in patients with rheumatoid arthritis in combination with a TNF inhibitor and methotrexate, with no new serious adverse effects being identified, researchers report (pp. 622–32). Adults with active RA were receiving stable doses of MTX and either etanercept or adalimumab. The 51 patients were randomized to receive one intravenous course of rituximab, as two doses of 500 mg, or placebo, with these results: “A serious infection (pneumonia) was observed in 1 patient (3%) in the rituximab group after 14.4 patient-years of exposure (6.95 events per 100 patient–years, 95% confidence interval 0.98–49.35), compared with none in the placebo group at week 24. Infections were reported in 18 patients (55%) and 11 patients (61%) in the rituximab and placebo groups, respectively. Grade 3 infections were reported in 3 patients (9%) receiving rituximab and in none of the patients receiving placebo. No grade 4 infections were observed, nor were there any opportunistic, fungal, or tuberculosis infections. Serious adverse events (SAEs) were reported in 2 rituximab-treated patients (pneumonia and coronary artery occlusion), whereas there were no SAEs reported in placebo-treated patients. At week 24, the percentage of patients achieving an American College of Rheumatology 20% (ACR20) improvement response was 30% in the rituximab group compared with 17% in the placebo group, and ACR50 responses were achieved by 12% and 6% of patients, respectively.” (M. W. Greenwald, mgreen@dc.rr.com)

>>>PNN NewsWatch
* FDA yesterday added a decade onto the approved age range for Zostavax vaccine (Merck), with people 50–59 years of age joining the over-60 group previously approved for using the shingles preventive.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 28, 2011 * Vol. 18, No. 59
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Mar. 27 issue of Lancet (2011; 377).
Tranexamic Acid in Bleeding Trauma: Early use of tranexamic acid is appropriate in patients with bleeding trauma, but for those admitted 3 hours or more after injury, the drug is less effective and could be harmful, according to results of the CRASH-2 trial (pp. 1096–202.e2). At 274 hospitals in 40 countries, 20,211 adult patients had these outcomes after treatment for bleeding trauma with tranexamic acid 1 g over 10 min followed by 1 g over 8 h or placebo: “10,096 patients were allocated to tranexamic acid and 10,115 to placebo, of whom 10,060 and 10,067, respectively, were analysed. 1,063 deaths (35%) were due to bleeding. We recorded strong evidence that the effect of tranexamic acid on death due to bleeding varied according to the time from injury to treatment (test for interaction p < 0.0001). Early treatment (≤1 h from injury) significantly reduced the risk of death due to bleeding (198/3,747 [5.3%] events in tranexamic acid group vs 286/3,704 [7.7%] in placebo group; relative risk [RR] 0.68, 95% CI 0.57–0.82; p < 0.0001). Treatment given between 1 and 3 h also reduced the risk of death due to bleeding (147/3,037 [4.8%] vs 184/2,996 [6.1%]; RR 0.79, 0.64—0.97; p = 0.03). Treatment given after 3 h seemed to increase the risk of death due to bleeding (144/3272 [4.4%] vs 103/3362 [3.1%]; RR 1.44, 1.12—1.84; p = 0.004). We recorded no evidence that the effect of tranexamic acid on death due to bleeding varied by systolic blood pressure, Glasgow coma score, or type of injury.” (Clinical Trials Unit, crash@lshtm.ac.uk)
Body Measures for Predicting Cardiovascular Risk: When clinical information is available for patients in developed countries, body measurements add little to models for predicting cardiovascular disease risk, researchers report (pp. 1085–95). Individual records from 58 cohorts were used to calculate these hazard ratios: “Individual records were available for 221,934 people in 17 countries (14,297 incident cardiovascular disease outcomes; 1.87 million person–years at risk). Serial adiposity assessments were made in up to 63,821 people (mean interval 5.7 years [SD 3.9]). In people with BMI of 20 kg/m2 or higher, HRs for cardiovascular disease were 1.23 (95% CI 1.17—1.29) with BMI, 1.27 (1.20—1.33) with waist circumference, and 1.25 (1.19—1.31) with waist-to-hip ratio, after adjustment for age, sex, and smoking status. After further adjustment for baseline systolic blood pressure, history of diabetes, and total and HDL cholesterol, corresponding HRs were 1.07 (1.03—1.11) with BMI, 1.10 (1.05—1.14) with waist circumference, and 1.12 (1.08—1.15) with waist-to-hip ratio. Addition of information on BMI, waist circumference, or waist-to-hip ratio to a cardiovascular disease risk prediction model containing conventional risk factors did not importantly improve risk discrimination (C-index changes of −0.0001, −0.0001, and 0.0008, respectively), nor classification of participants to categories of predicted 10-year risk (net reclassification improvement −0.19%, −0.05%, and −0.05%, respectively). Findings were similar when adiposity measures were considered in combination. Reproducibility was greater for BMI (regression dilution ratio 0.95, 95% CI 0.93–0.97) than for waist circumference (0.86, 0.83–0.89) or waist-to-hip ratio (0.63, 0.57–0.70).” (Emerging Risk Factors Collaboration Coordinating Ctr., erfc@phpc.cam.ac.uk)

>>>PNN NewsWatch
* FDA has approved ipilimumab (Yervoy, Bristol-Myers Squibb) for treatment of patients with unresectable or metastatic melanoma. The agent, which acts by blocking cytotoxic T-lymphocyte antigen-4, is the first to show a significant improvement in overall survival with this highly fatal condition.

>>>PNN JournalWatch
* Genomics and Drug Response, in New England Journal of Medicine, 2011; 364: 1144–53. (R. M. Weinshilboum, weinshilboum.richard@mayo.edu)
* American Society of Clinical Oncology Executive Summary of the Clinical Practice Guideline Update on the Role of Bone-Modifying Agents in Metastatic Breast Cancer, in
Journal of Clinical Oncology, 2011; 29: 1221–7. (American Society of Clinical Oncology, guidelines@asco.org)
* Relationship Between Oral Antihyperglycemic Medication Adherence and Hospitalization, Mortality, and Healthcare Costs in Adult Ambulatory Care Patients with Type 2 Diabetes in South Korea, in
Medical Care, 2011; 49: 378–84. (J. S. Hong)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 29, 2011 * Vol. 18, No. 60
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Mar. 28 issue of the Archives of Internal Medicine (2011; 171).
Carotene Levels & Mortality: People with higher levels of serum alpha-carotene have lower rates of all-cause mortality and risks of death from cardiovascular conditions, cancers, and other causes, researchers report (pp. 507–15). Using data from the Third National Health and Nutrition Examination Survey Follow-up Study, investigators found these patterns among 15,318 American adults: “Compared with participants with serum alpha-carotene concentrations of 0 to 1 µg/dL (to convert to micromoles per liter, multiply by 0.01863), those with higher serum levels had a lower risk of death from all causes (P < .001 for linear trend): the relative risk for death was 0.77 (95% confidence interval, 0.68-0.87) among those with alpha-carotene concentrations of 2 to 3 µg/dL, 0.73 (0.65–0.83) among those with concentrations of 4 to 5 µg/dL, 0.66 (0.55–0.79) among those with concentrations of 6 to 8 µg/dL, and 0.61 (0.51–0.73) among those with concentrations of 9 µg/dL or higher after adjustment for potential confounding variables. We also found significant associations between serum alpha-carotene concentrations and risk of death from CVD (P = .007), cancer (P = .02), and all other causes (P < .001). The association between serum alpha-carotene concentrations and risk of death from all causes was significant in most subgroups stratified by demographic characteristics, lifestyle habits, and health risk factors.” (C. Li, cli@cdc.gov)
Use of Personal Health Records: Race/ethnicity and income levels form a “digital divide” when it comes to adoption of personal health records (PHRs), according to a study conducted in a northeastern health system (pp. 568–74). The cross-sectional analysis compared adopters (those activating a PHR account online) with nonadopters (those who see a physician offering the PHR but do not activate an account): “As of September 30, 2009, among 75,056 patients, 43% had adopted the PHR since 2002. Blacks and Hispanics were less likely to adopt the PHR compared with whites (odds ratio [OR], 0.50; 95% confidence interval [CI], 0.45–0.55; and 0.64; 0.57–0.73, respectively), and those with lower annual income were less likely to adopt the PHR than were those with higher income. Compared with nonadopters, adopters were more likely to have more than 2 comorbidities (OR, 1.27; 95% CI, 1.17–1.30). Use of an aggressive marketing strategy for PHR enrollment increased adoption nearly 3-fold (OR, 2.92; 95% CI, 1.58–5.40). Intensity of use was best predicted by increasing number of comorbidities, followed by race/ethnicity (whites more than blacks and Hispanics) and insurance status. We found no association between income and log-in frequency or secure messages sent.” (D. W. Bates, dbates@partners.org)
“Training Patients” & Cardiovascular-Device Research: In investigational research on cardiovascular devices, exclusion of training patients—the first patients in whom physicians use a device—may bias results in favor of the device, a study claims (pp. 534–9). Based on data from FDA submissions in 2000–07, investigators determined: “There were 78 cardiovascular device summaries in this 8-year period, of which 17 (22%) involved training patients. Of the 123 studies in the summaries, 20 (16%) used training patients. All studies excluded training patients from efficacy analyses and 19 of 20 (95%) excluded them from safety analyses. Sixteen of 20 (80%) did not provide any outcome data, and 15 of 20 (75%) did not check for outcome differences between training and nontraining treatment patients. Eighteen of 20 (90%) did not provide demographic information on training patients, and 14 of 20 (70%) did not prespecify guidelines for their enrollment.” (R. F. Redberg, redberg@medicine.ucsf.edu)

>>>PNN NewsWatch
* Policies on potential conflicts of interest, pharmacists’ roles in health care reform, and accreditation of pharmacies were adopted by the APhA House of Delegates, meeting yesterday before APhA2011 closed in Seattle. Three of six new business items were also adopted at the APhA Annual Meeting & Exposition, including statements that supported mandatory influenza vaccination of pharmacy personnel, obtaining provider status for pharmacists under the Social Security Act, and encouraging collaboration with the American Public Health Association, pharmacist.com reports.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 30, 2011 * Vol. 18, No. 61
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Early-release article from JAMA (2011; 305).
Interactive Games to Promote Behavior Change: Interactive games, developed properly, hold promise for effecting behavioral change for preventing and treating disease, according to authors of a Commentary article (doi: 10.1001/jama.2011.408). Software development could build on the success of games such as Packy & Marlon, which simulates type 1 diabetes, and the Wii exergame console: “The substantial growth of new interactive game technologies and genres raises new concerns and opportunities. The size and level of engagement of the audience means that health games can affect a wide range of individuals, including those who are difficult to reach with traditional messaging. Powerful technology can also have unintended consequences. Exercise games could work too well and lead to cardiovascular or joint complications. Failure of motivational games could lead to disillusionment and disengagement.
“This is just the early stage of knowing how to create and deploy applications that actually deliver health benefits. Additional investigation is necessary to determine whether and how to integrate effective interactive games into clinical care settings and community programs without disrupting trusted relationships with clinicians. To create the foundation for evidence-based design, use, and refinement of these promising technologies, further studies will need to address questions about mechanism of action, efficacy, and safety across the range of uses and participant demographics. In the meantime, those offering health games should at least make the key design principles and objectives available to health professionals to enable a common-sense evaluation of suitability.” (J. L. Read,
leighton@alloyventures.com)

>>>Diabetes Highlights
Source:
Apr. issue of Diabetes Care (2011; 34).
Testosterone Replacement in Type 2 Diabetes/Metabolic Syndrome: In hypogonadal men with type 2 diabetes and/or metabolic syndrome (MetS), testosterone replacement therapy (TRT) had beneficial effects on insulin resistance, total and LDL-cholesterol, lipoprotein a, and sexual health, researchers report (pp. 828–37). Transdermal 2% testosterone gel was evaluated for 12 months in 220 men, with randomization for 6 months and medication changes allowed in months 6–12: “TRT reduced [homeostasis model assessment of insulin resistance] in the overall population by 15.2% at 6 months (P = 0.018) and 16.4% at 12 months (P = 0.006). In type 2 diabetic patients, glycemic control was significantly better in the TRT group than the placebo group at month 9 (HbA1c: treatment difference, −0.446%; P = 0.035). Improvements in total and LDL cholesterol, lipoprotein a, body composition, libido, and sexual function occurred in selected patient groups. There were no significant differences between groups in the frequencies of adverse events (AEs) or serious AEs. The majority of AEs (>95%) were mild or moderate.” (T. H. Jones, hugh.jones@nhs.net)
Smoking & Incident Diabetes: In the Nurses’ Health Study, passive or active smoke exposure increased the risk of incident type 2 diabetes (pp. 892–7): “Compared with nonsmokers with no exposure to passive smoke, there was an increased risk of diabetes among nonsmokers who were occasionally (relative risk [RR] 1.10 [95% CI 0.94–1.23]) or regularly (1.16 [1.00–1.35]) exposed to passive smoke. The risk of incident type 2 diabetes was increased by 28% (12–50) among all past smokers. The risk diminished as time since quitting increased but still was elevated even 20–29 years later (1.15 [1.00–1.32]). Current smokers had the highest risk of incident type 2 diabetes in a dose-dependent manner. Adjusted RRs increased from 1.39 (1.17–1.64) for 1–14 cigarettes per day to 1.98 (1.57–2.36) for ≥25 cigarettes per day compared with nonsmokers with no exposure to passive smoke.” (L. Zhang, nhlzh@channing.harvard.edu)

>>>PNN NewsWatch
* Because moisture can cause dabigatran etexilate mesylate (Pradaxa, Boehringer Ingelheim) to break down and lose potency, the product should be dispensed and stored in the original bottle or blister packaging, FDA cautioned yesterday. Patients should be aware of this requirement and the need to discard any unused product remaining 30 days after the seal is broken.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.

PNN Pharmacotherapy Line
Mar. 31, 2011 * Vol. 18, No. 62
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Mar. 31 issue of the New England Journal of Medicine (2011; 364).
Boceprevir for Hepatitis C Virus: Two research articles and an editorial explore use of a linear peptidomimetic ketoamide serine protease inhibitor, boceprevir, in patients with chronic infections of hepatitis C virus (HCV) genotype 1.
Addition of boceprevir to standard therapy with peginterferon alfa-2b–ribavirin, as compared with standard therapy alone, significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection, researchers report (
pp. 1195–206). Following a 4-week lead-in period of treatment with peginterferon plus ribavirin, group 1 control patients continued on this therapy for 44 weeks. Group 2 received boceprevir plus peginterferon–ribavirin for 24 weeks, after which those with earlier detectable HCV levels were switched to placebo plus peginterferon–ribavirin for the last 20 weeks. Group 3 patients received boceprevir plus peginterferon–ribavirin for 44 weeks, as follows: “A total of 938 nonblack and 159 black patients were treated. In the nonblack cohort, a sustained virologic response was achieved in 125 of the 311 patients (40%) in group 1, in 211 of the 316 patients (67%) in group 2 (P < 0.001), and in 213 of the 311 patients (68%) in group 3 (P < 0.001). In the black cohort, a sustained virologic response was achieved in 12 of the 52 patients (23%) in group 1, in 22 of the 52 patients (42%) in group 2 (P = 0.04), and in 29 of the 55 patients (53%) in group 3 (P = 0.004). In group 2, a total of 44% of patients received peginterferon–ribavirin for 28 weeks. Anemia led to dose reductions in 13% of controls and 21% of boceprevir recipients, with discontinuations in 1% and 2%, respectively.” (F. Poordad, fred.poordad@cshs.org)
Similar results were obtained in 403 previously treated patients, with boceprevir producing higher rates of sustained virologic responses, compared with peginterferon–ribavirin (
pp. 1207–17). The same group methodology as in the above study was used, except that group 2 was continued on boceprevir plus peginterferon–ribavirin through week 32, at which point patients whose week-8 HCV RNA level was detectable had placebo substituted for boceprevir. Results showed: “The rate of sustained virologic response was significantly higher in the two boceprevir groups (group 2, 59%; group 3, 66%) than in the control group (21%, P < 0.001). Among patients with an undetectable HCV RNA level at week 8, the rate of sustained virologic response was 86% after 32 weeks of triple therapy and 88% after 44 weeks of triple therapy. Among the 102 patients with a decrease in the HCV RNA level of less than 1 log10 IU per milliliter at treatment week 4, the rates of sustained virologic response were 0%, 33%, and 34% in groups 1, 2, and 3, respectively. Anemia was significantly more common in the boceprevir groups than in the control group, and erythropoietin was administered in 41 to 46% of boceprevir-treated patients and 21% of controls.” (B. R. Bacon, baconbr@slu.edu)
“HCV protease inhibitors represent a major advance in our ability to treat chronic HCV infection,” writes an editorialist (
pp. 1272–4). “Future therapy will be more complex, not easier, but the improvement in the rate of sustained virologic response with boceprevir, to nearly 70% in the SPRINT-2 trial and to more than twice the rate in previously treated patients in HCV RESPOND-2, have been eagerly awaited. We will soon embark on a new era of successful HCV therapy.” (D. M. Jensen)

>>>PNN NewsWatch
* An outbreak of 19 cases of Serratia marcescens bacteremia at six Alabama hospitals has been traced to contamination of TPN fluids at Meds IV, a compounding pharmacy, FDA said in a MedWatch announcement. Meds IV has ceased operations and recalled all of its IV compounded products, the Alabama Department of Public Health said.
*
FDA yesterday acknowledged a continuing role for compounding pharmacists in preparation of hydroxyprogesterone caproate injection products “based on a valid prescription for an individually identified patient.” The agency on Feb. 3 had approved Makena, a KV Pharmaceuticals formulation. However, FDA said, it will allow continued compounding of the agent, given the “unique situation” and “to support continued access to this important drug,” so long as compounded products meet safety and quality standards.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2011, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at http://homepage.mac.com/lmposey/PNN.